Artificial Intelligence is increasingly being used by social media platforms to tackle online hate speech. The sheer quantity of content, the speed at which is it developed and the enhanced pressure companies are facing by States to remove hate speech quickly from their platforms have led to a tricky situation. This commentary argues that automated mechanisms, which may have biased datasets and be unable to pick up on the nuances of language, should not be left unattended with hate speech as this can lead to issues of violating freedom of expression and the right to non-discrimination.

The literature lacks consensus on the minimum microbial density required for diagnosing urinary tract infections (UTIs). This study categorized the microbial densities of urine specimens from symptomatic presumptive UTI patients and correlated them with detected levels of immune response biomarkers NGAL, IL-8, and IL-1β. The objective was to identify changes in immune response at different microbial densities and determine an optimal threshold for diagnosing symptomatic UTIs. Midstream clean-catch urine samples were analyzed for microbial identification and quantification using SUC and M-PCR, while NGAL, IL-8, and IL-1β levels were measured with ELISA. NGAL, IL-8, and IL-1β levels were all significantly higher in symptomatic subjects with microbial densities ≥ 10,000 cells/mL by M-PCR (p < 0.0069) or equivalent CFUs/mL by SUC (p < 0.0104) compared to samples with no detectable microbes. With both PCR and SUC, a consensus of two or more elevated biomarkers correlated well with microbial densities > 10,000 cells/mL or CFU/mL, respectively. The association between ≥ 10,000 cells and CFU per mL with elevated biomarkers in symptomatic patients suggests that this lower threshold may be more suitable for diagnosing UTIs. These findings challenge the widely used threshold of 100,000 CFU per mL, which may overlook many active UTI cases.

The theory of the continuous two-dimensional (2D) Fourier Transform in polar coordinates has been recently developed but no discrete counterpart exists to date. In this paper, we propose and evaluate the theory of the 2D discrete Fourier Transform (DFT) in polar coordinates. This discrete theory is shown to arise from discretization schemes that have been previously employed with the 1D DFT and the discrete Hankel Transform (DHT). The proposed transform possesses orthogonality properties, which leads to invertibility of the transform. In the first part of this two-part paper, the theory of the actual manipulated quantities is shown, including the standard set of shift, modulation, multiplication, and convolution rules. Parseval and modified Parseval relationships are shown, depending on which choice of kernel is used. Similar to its continuous counterpart, the 2D DFT in polar coordinates is shown to consist of a 1D DFT, DHT and 1D inverse DFT.

The space time fractional Korteweg-de Vries equation, modified Equal Width equation and Benney-Luke Equations are solved by using simple hyperbolic tangent Ansatz method. A simple compatible wave transformation in one dimension is employed to reduce the governing equations to integer ordered ODEs. Then, the ansatz approximation is used to derive exact solutions. Some illustrative examples are presented for some particular choices of parameters and derivative orders.

Asthma is characterized by mucus abnormalities. Airway epithelial metaplasia results in changes in stored and secreted mucin and the production of a pathologic mucus gel. Mucus transport is impaired culminating in mucus plugging and airway obstruction, a major cause of morbidity in asthma. The polymeric mucins MUC5AC and MUC5B are integral components of airway mucus. MUC5AC and MUC5B gene expression is altered in asthma and recent work sheds light on their contribution to asthma pathogenesis. Herein we review our current understanding of the role of MUC5AC and MUC5B in mucus dysfunction in asthma.

Background: Water treadmill (WT) exercise is a popular modality for the training and rehabilitation of horses. However, evidence-based literature regarding the use of WT exercise, particularly using inclines, is lacking.Objectives: The aim of this study was to assess the effect of recurring inclined WT sessions on equine epaxial muscles development.Methods: Six horses completed 24 sessions of 15 minutes of WT activity over four weeks. Horses walked with water at mid-cannon level at a treadmill incline of 4%. Back traces were measured at three and seven centimetres ventral to the dorsal midline at T5, T9, T14 and T18, prior to the first session (W0) and weekly for 4 weeks (W1-4). Results: Overall the back traces demonstrated progressive increases in muscle development (p<0.05), starting at W2 up to W4. At three centimetres ventral to the dorsal midline the most to least significant increases in gross muscle development were at T18, T5, T9 and T14, respectively and when measured at seven centimetres ventrally, the most to least significant increases were demonstrated at T5, T18 and T14 . It was noted that increases in thoracic back profile musculature were mainly observed within two to four weeks of the WT intervention.Conclusions: It has been concluded that repeated WT exercise on an incline setting has a significant effect on the rate and size of growth of equine thoracic back profile musculature. Muscle hypertrophy due to resistance training in the WT starts at 2 weeks within the programme, and it progresses as exercise continues to be performed.

We aimed to determine if infection-associated urine biomarkers can differentiate true urinary tract infection (UTI) from non-UTI controls. Midstream clean-catch urine samples were collected from asymptomatic volunteers and symptomatic subjects > 60 years old diagnosed with presumptive UTI in a specialty setting. Microbial identification and density were assessed using multiplex PCR/pooled antibiotic susceptibility test (M-PCR/P-AST) and standard urine culture (SUC). Three biomarkers (NGAL, IL-8, and IL-1β) were measured in the same urine specimens. Definitive UTI cases were symptomatic and had positive microorganism detection by SUC and M-PCR, while definitive non-UTI cases were asymptomatic volunteers regardless of microbial detection. We observed a strong positive correlation (R2 ≈ 1) between microbial density and the biomarkers NGAL, IL-8, and IL-1β. Biomarker consensus criteria of two or more positive biomarkers had sensitivity 90.2%, specificity 91.2%, positive predictive value (PPV) 91.7%, negative predictive value (NPV) 89.7%, accuracy 90.7%, positive likelihood ratio of 10.28, and negative likelihood ratio of 0.11 in differentiating definitive UTI from non-UTI cases, regardless of microbial density. NGAL, IL-8, and IL-1β showed a significant elevation in symptomatic cases with positive microbe identification compared to asymptomatic cases with or without microbe identification. Biomarker consensus exhibited high accuracy in distinguishing UTI from non-UTI cases.

Growing crystals of nickel niobate (NiNb2O6), we noticed that changing growth conditions allowed our material to enter different areas of the phase diagram. In particular, we found that excess material accumulated within and above the liquid zone. Analysis showed that this was an unincorporated constituent. Changing the ratio of the constituent oxides - an excess of ~4% of either NiO or Nb2O5 gave us the opportunity to investigate changes in zone stability, melting temperature and quality of the resulting crystal. We found that a small excess of nickel oxide decreases the melting temperature significantly, and created the best pseudo-rutile NiNb2O6 crystal studied, while higher amounts of niobium oxide allowed us to stabilize the NiNb2O6 columbite phase. This research reinforces the idea that self-flux as a travelling solvent can significantly impact crystal growth parameters and quality.

Stress mechanisms have long been associated with neuronal loss and neurodegenerative diseases. The origin of cell stress and neuronal loss likely stems from multiple pathways. These include (but are not limited to) bioenergetic failure, neuroinflammation, and loss of proteostasis. Cells have adapted compensatory mechanisms to overcome stress and circumvent death. One mechanism is mitophagy. Recent studies have implicated mitophagy in several neurodegenerative diseases and clinical trials are underway which target mitophagy pathways. Here, we review mitophagy pathways, the role of mitophagy in neurodegeneration, potential therapeutics, and the need for further study.

Obesity is one of the most prevalent health conditions in humans and companion animals across the world. Obesity is associated with multiple health conditions across species including premature mortality. It is therefore of importance across the fields of medicine and veterinary medicine. The regulation of body weight is a homeostatic process vulnerable to disruption by genetic and environmental factors. It is well established that the heritability of obesity is high in humans and laboratory animals, with ample evidence that the same is true in companion animals. In this review, we provide an overview of how genes link to obesity in humans, drawing on a wealth of information from laboratory animal models, and summarising the mechanisms by which obesity causes related disease. Throughout, we focus on how large-scale human studies and niche investigations of rare mutations in severely affected patients have improved our understanding of obesity biology and can inform our ability to interpret results of animal studies. For dogs, cats and horses, we review the similarities in obesity pathophysiology to humans and review those genetic studies that have been done to investigate them. Finally, we discuss how veterinary genetics may learn from humans about studying precise, nuanced phenotypes and implementing large-scale studies, but also how veterinary studies may be able to look past clinical findings to mechanistic ones and demonstrate translational benefits to human research.

For the numerical simulation of components made of short fiber-reinforced composites the correct prediction of the deformation including the elastic and plastic behavior and its spatial distribution is essential. When using purely deterministic modeling approaches the information of the probabilistic microstructure is not included in the simulation process. One possible approach for the integration of stochastic information is the use of random fields. In this study numerical simulations of tensile test specimens are conducted utilizing a finite deformation elastic-ideal plastic material model. A selection of the material parameters covering the elastic and plastic domain are represented by cross-correlated second-order Gaussian random fields to incorporate the probabilistic nature of the material parameters. To validate the modeling approach tensile tests until failure are carried out experimentally, that confirm the assumption of spatially distributed material behavior in both the elastic and plastic domain. Since the correlation lengths of the random fields cannot be determined by pure analytic treatments, additionally numerical simulations are performed for different values of the correlation length. The numerical simulations endorse the influence of the correlation length on the overall behavior. For a correlation length of 5mm a good conformity with the experimental results is obtained. Therefore, it is concluded, that the presented modeling approach is suitable to predict the elastic and plastic deformation of a set of tensile test specimens made of short fiber-reinforced composite sufficiently.

The theory of the continuous two-dimensional (2D) Fourier Transform in polar coordinates has been recently developed but no discrete counterpart exists to date. In the first part of this two-paper series, we proposed and evaluated the theory of the 2D discrete Fourier Transform (DFT) in polar coordinates. The theory of the actual manipulated quantities was shown, including the standard set of shift, modulation, multiplication, and convolution rules. In this second part of the series, we address the computational aspects of the 2D DFT in polar coordinates. Specifically, we demonstrate how the decomposition of the 2D DFT as a DFT, Discrete Hankel Transform (DHT) and inverse DFT sequence can be exploited for efficient code. We also demonstrate how the proposed 2D DFT can be used to approximate the continuous forward and inverse Fourier transform in polar coordinates in the same manner that the 1D DFT can be used to approximate its continuous counterpart.

This paper presents a novel improvement of MuSIASEM (Multiscale Integrated Analysis of the Societal and Ecological Metabolism) by incorporating a new regional analysis of the electricity metabolism across levels. An analysis of Mexico illustrates this toolkit and shows that the industry sector had Economic Energy Intensity (EEI) with 40.3 MWh/MMXN reached a higher value than the commerce and services sector with 0.84 MWh/MMXN. Regarding the Economic Labor Productivity (ELP) indicator (AV/h), the industrial sector with 208.5 TMXN/Kh reached a higher value than the Commercial and services sector with 114.3 TMXN/Kh. With reference to the Exosomatic Metabolic Rate (EMR), the Household sector obtained 59.3 KWh/Kh whereas the paid sector reached 2,486.4 KWh/Kh. Disaggregation of the EMR indicator into economic sectors shows that the Industrial sector obtained 8.4 KWh/Kh and the commercial and services sector reached 0.10 KWh/Kh. The lack of complete data for the agricultural sector does not allow us to calculate EEI, ELP, and EMR indicators accurately. Considering the analysis of indicators by regions, regarding the EEI rate, the Central region had the lowest value with 12.7 MWh/MMXN, followed by the Northeast with 21.4 MWh/MMXN and Western with 29.4 MWh/ MMXN, which means that they require less electricity to produce more added value. In terms of the ELP indicator, it was found regions with higher values were Northeast with 182.3 MMXN/Mh, Central with 177.5 MMXN/Mh, and North with 127 MMXN/Mh, which means that these regions produce more added value per hour of work. About the EMR, it is observed that regions in the northern part of the country had higher values: Northwest with 337 KWh/Kh, Baja California Sur with 334 KWh/Kh, Baja California with 328 KWh/Kh, North with 313 KWh/Kh and Northeast with 274 KWh/Kh, which means that these regions consume more electricity per hour. This innovative approach is useful for governance because it helps to understand and reduce asymmetries across regions, resulting in more social equality and a better economic equilibrium across sectors and regions.

Despite increased hurricane intensity, the U.S. Gulf of Mexico coast has experienced dramatic coastal population increase of 24.5% from 2000 to 2016. However, in coastal Louisiana areas with dramatic wetland loss, parishes have experienced population declines and lower rates of population growth. Therefore, understanding the magnitude of the effect of wetland loss as a main driver in population loss in coastal Louisiana is critical. Using regression analysis, this study finds that wetland loss has a significant and persistent negative effect on population growth in coastal Louisiana. This effect resulted in a reduction in the population growth rate in coastal parishes over time. A counterfactual simulation was conducted to estimate the potential population size in the absence of wetland loss from 1990 to 2021. On average, the effect of 1 hectare of wetland lost causes a reduction of approximately 1000 persons. This indicates that for the year 2021, the population was approximately 18% lower than the population that would have existed in the absence of wetland loss. This research underscores the role of wetlands in providing direct and indirect benefits to people in coastal Louisiana that are ultimately reflected in its population levels.

Platelets are a uniquely mammalian physiologic attribute. As the only non-marine vertebrate class to experience menopause, humans have a substantial post-reproductive lifespan and are believed to have a limited, non-renewable oocyte supply. Ovarian reserve typically declines after about age 35yrs, marking losses which cannot be recovered by available fertility medications. When in vitro fertilization fails due to low or absent ovarian response, gonadotropin adjustments are often ineffectual and if additional oocytes are occasionally harvested, egg quality is usually poor. This problem was confronted by Greek researchers who developed a new surgical method to insert autologous platelet-rich plasma (PRP) into ovaries; the first ovarian PRP success to improve reproductive outcomes was published from Athens in 2016. This innovation influenced later research with condensed platelet-derived growth factors, leading to correction of oocyte ploidy error, normal blastocyst development, and additional term livebirths. Yet women’s health was among the last clinical domains to explore PRP, and its role in ‘ovarian rejuvenation’ remains unsettled. One critical aspect in this procedure is platelet activation, a commonly overlooked step in the cytokine release cascade considered essential for successful transition of undifferentiated ovarian stem cells to an oocyte lineage. Poor activation of platelets thus becomes an unforced error, potentially diminishing or even negating post-treatment ovarian follicular response. To answer this query, relevant theory, current disagreements, and new data on platelet activation are presented, along with clinical challenges for regenerative fertility practice.

As a prominent organizational issue there was limited evidence in the literature about the relationship between organizational strategy, workplace health, safety, and wellbeing, and performance measurement that demonstrate a measurable impact on organizational performance. Whilst the literature reports numerous studies into the relationship between employee engagement and performance, they hardly incorporate workplace health, safety, and well-being within this relationship. This mixed-methods study investigated the relationship between organizational strategy, workplace health, safety, and wellbeing strategy, employee engagement, and strategy efficacy from a corporate perspective. Findings from Phase two, the online survey, revealed a seven-factor HSW Strategy framework. The workplace health, safety, and wellbeing strategy framework provide empirical evidence towards a suitable and valuable framework for high-risk businesses to improve individual and organizational performance.

In this study, we described the most critical risk factors for different malignancies including: breast, prostate, lung, and colorectal carcinoma among others, with an emphasis on modifiable risk factors. We revised the literature review about risk factors involved in the genesis of cancer in various databases, including articles indexed in PUBMED, SCOPUS, PMC, and Google Scholar. Awareness of risk factors enables conscious decisions to be made in an effort to combat malignancies. Knowing risk factors is a mode of fighting malignancy. Diet, lifestyle, practises, and laboratory/clinical interventions were among risk factors of diverse malignancy. Diet, lifestyle, laboratory/clinical interventions all contribute to the genesis and prognosis in a variety of malignancies. We concluded that abstaining from risk factors can prevent the development of many malignancies in a century where this conundrum is raising disproportionately. By informing the public about modifiable risk factors cancer mortality rates can be reduced. It is treated here is to make the public aware of the modifiable risks of cancers.

Understanding mechanisms of ageing remains a complex challenge for biogerontologists, but recent adaptations of evolutionary ageing theories offer a compelling lens in which to view both age-related molecular and physiological deterioration. Ageing is commonly associated with a progressive loss of biochemical processes and degeneration of molecular material, however, the mechanisms of diminishing function are not simply a result of aberrant expression of these pathways. Natural selection pressures are at their highest in youthful periods to select genes advantageous to maximising reproductive capacity. After sexual maturation, selective pressure diminishes, subjecting individuals to maladaptive pleiotropic gene function once beneficial for developmental growth, but pathogenic later in life. Due to this selective ‘shadowing’ in ageing, mechanisms to counter hyperfunctional genes are unlikely to evolve within a given species. These genetic ‘run-on’ programmes are not dysfunctional per se and, in fact, remain highly robust. Thus, interventions capable of optimising gene function during the ageing process represent as attractive therapeutic modalities. Caenorhabditis elegans offers a unique model to explore high-throughput screening of interventions to combat hyperfunctional pathways involved in ageing. However, the majority of research to date employ whole-life vs late-life pathway manipulation of developmental/growth-related systems to claim ageing attenuation, despite significant impairments in early-life fitness and discordance with healthspan. Here, we discuss data supporting hyperfunctional changes at a global molecular and functional level in C. elegans, and how classical lifespan-extension mutants alter these dynamics. We later discuss the relevance of such mutant models for exploring mechanisms of ageing, highlighting that post-reproductive gene manipulation represents a far more translatable approach for C. elegans research not routed within pleiotropic constraints. More so, lifespan has become a routine readout for quantifying ‘ageing’, however, we make the argument that a compression of gerospan vs lifespan extension is a more meaningful goal for anti-ageing regimes with current knowledge. Similarly, mechanisms governing lifespan are distinct from those regulating health, and slowing senescent pathology accumulation appears more applicable for the abstraction to human ageing.

In critically ill patients with COVID-19, concomitant abnormalities of coagulation have been seen with an unusually high incidence. Standard coagulation tests are limited in their ability accurately to reflect the severity of the pro-thrombotic phenotype observed in severe COVID-19 infections. In this narrative review we consider the role of rotational thromboelastometry (ROTEM) as a near bedside test allowing a more comprehensive assessment of haemostatic function in the context of COVID-19 infection. Comprehensive literature search was conducted on PubMed, revealing 13 publications on the subject. The coagulopathy of this disease process appears to be insufficiently represented with often normal conventional coagulation test parameters. Whilst not the perfect substitute for in vivo coagulation, studies utilising rotational thromboelastometry assays in COVID-19 patients have demonstrated increased maximum clot firmness (consistent with hyper-coagulability) and reduced maximum lysis (consistent with “fibrinolytic shutdown”). ROTEM appears to be a possible tool for risk stratification and to monitor the potential modulation of fibrinogen-dependent coagulation processes with enhanced anti-coagulation strategies. Precisely how these coagulation abnormalities can be modified by optimum, individualised medical interventions to improve clinical outcome, however, remains unclear.

Tracking the kinematics of human movement usually requires the use of equipment that constrains the user within a room (e.g., optical motion capture systems), or requires the use of a conspicuous body-worn measurement system (e.g., inertial measurement units (IMUs) attached to each body segment). This paper presents a novel Lie group constrained extended Kalman filter to estimate lower limb kinematics using IMU and inter-IMU distance measurements in a reduced sensor count configuration. The algorithm iterates through the prediction (kinematic equations), measurement (pelvis height assumption/inter-IMU distance measurements, zero velocity update for feet/ankles, flat-floor assumption for feet/ankles, and covariance limiter), and constraint update (formulation of hinged knee joints and ball-and-socket hip joints). The knee and hip joint angle root-mean-square errors in the sagittal plane for straight walking were 7.6±2.6∘ and 6.6±2.7∘, respectively, while the correlation coefficients were 0.95±0.03 and 0.87±0.16, respectively. Furthermore, experiments using simulated inter-IMU distance measurements show that performance improved substantially for dynamic movements, even at large noise levels (σ=0.2 m). However, further validation is recommended with actual distance measurement sensors, such as ultra-wideband ranging sensors.

The contribution of genetic and environmental factors to the pathophysiology of cerebral aneurysms in monozygotic twins is under-reported and presents ambiguous arguments. The morphology and hemodynamics of neurovascular arteries in a pair of monozygotic twins (MTs) were investigated to reveal the underlying mechanisms. Four arterial models were reconstructed for the twin A-right brain and left brain, twin B-left brain, and B-left brain without anterior cerebral arteries based on preclinical scanned information. Subsequently, the dimensions, configurations and outlined curves of the three-perspective geometries were compared between the MTs. Adopting an in-vitro validated numerical cerebral aneurysm model, hemodynamic patterns were investigated and compared in the MT models, respectively. Morphological comparisons of the MTs show the size and shape of cerebral arteries exist significant differences, despite of the expected genetic similarities. These differences can be attributed to variations during embryological development and external environmental influences. Qualitatively and generally, numerical results indicate the MTs have some hemodynamic similarities (e.g., time-averaged pressure (TAP) distributions (~13400 Pa), and oscillatory shear index (0~0.49), but present significant differences in specific local arteries due to morphological variances. Specifically, the difference in the volumetric blood flow rate in corresponding arteries between the MTs is from 16% (smallest) in anterior choroidal artery (AChA) to 221% (largest) in the ophthalmic artery (OphA), varying with specific compared arteries. Also, the registered hemodynamic indicators, such as the maximum time-averaged wall shear stress (TWSS) (53.6 Pa vs. 37.8 Pa), and different local OSI distributions were observed between the MTs. The findings revealed that morphological variations in MTs could be generated by embryological and environmental factors, thus assuming they share the identical morphology in cardiovascular and neurovascular systems may lead to significant misevaluations in hemodynamics quantifications and further lesions.

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca2+) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD, however it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess early calcium and glutamate phenotypes of FAD by measuring the Ca2+ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA and kainate compared to isogenic control and healthy lines. The data shows that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca2+ responses to glutamate and AMPA, but not NMDA or kainate. Together this suggests that PSEN1 mutations alter Ca2+ and glutamate signaling as an early phenotype of FAD.

At 8000 m and above, a ‘death zone’ reputation afforded protection for the fragile ecosystems of the Himalaya and Korakoram ranges for thousands of years. After decades of high-altitude mountaineering, environmental impacts have been documented such as associated carbon-intensive air travel and contamination from waste. Despite the growing popularity, high-risk and fragile context of the sport, the behaviour, perspectives and experiences of high-altitude mountaineers, and the social and economic consequences have not been researched. Following an interpretive paradigm and using purposive sampling, this qualitative study conducted in-depth interviews and open-ended survey questions to collect the experiences of sixteen high-altitude mountaineers. Analysis of the qualitative data was informed by Grounded Theory with the coding process leading to the overarching category of ‘leave no trace’. The results show how the high risks to life, and growing popularity of the activity influence mountaineer’s ability to act sustainably and increase unsustainable behaviour despite a desire to ‘leave no trace’ on the mountain. Meanwhile, climate change has already and will increasingly have profound impacts on the risks associated with 8000m mountaineering. Allowing more time for acclimation would help to address the root causes of unsustainable behaviours along with better enforcement of regulations.

Neurologic disorders such as traumatic brain injury, multiple sclerosis, Alzheimer’s disease, and drug-resistant epilepsy have a high socioeconomic impact around the world. Current therapies for these disorders are often not effective. This creates a demand for the development of new therapeutic approaches to treat these disorders. Recent data suggest that autoreactive naturally occurring immunoglobulins produced by subsets of B cells called B1 B cells combined with complement are actively involved in the processes of restoration of neuronal functions during pathological conditions and remyelination. The focus of this review is to discuss the possibility of creating specific therapeutic antibodies that can activate and fix complement to enhance neuronal survival and promote central nervous system repair after injuries associated with many types of neurodegenerative diseases.

Cellular agriculture is defined as the production of agricultural products from cell cultures rather than from whole plants or animals. With growing interest in cellular agriculture as a means to address the public health, environmental, and animal welfare challenges of animal agriculture, the concept of producing seafood from fish cell- and tissue-cultures is emerging as a means to address similar challenges with industrial aquaculture systems and marine capture. Cell-based seafood - as opposed to animal-based seafood - can combine developments in biomedical engineering with modern aquaculture techniques. Biomedical engineering developments such as closed-system bioreactor production of land animal cells create a basis for large scale production of marine animal cells. Aquaculture techniques such as genetic modification and closed system aquaculture have achieved marked gains in production that can pave the way for innovations in cell-based seafood production. Here, we present the current state of innovation relevant to the development of cell-based seafood across multiple species as well as specific opportunities and challenges that exist for advancing this science. The authors find that the physiological properties of fish cell- and tissue- culture may be uniquely suited to cultivation in vitro. These physiological properties, including hypoxia tolerance, high buffering capacity, and low-temperature growth conditions, make marine cell culture an attractive opportunity for scale production of cell-based seafood; perhaps even more so than mammalian and avian cell cultures for cell-based meats. This, coupled with the unique capabilities of crustacean tissue-friendly scaffolding such as chitosan, a common seafood waste product and mushroom derivative, presents great promise for cell-based seafood production via bioreactor cultivation. To become fully realized, cell-based seafood research will require more understanding of fish muscle culture and cultivation; more investigation into serum-free media formulations optimized for fish cell culture; and bioreactor designs tuned to the needs of fish cells for large scale production.

Microsamples (collections usually less than 50 µL) have been introduced in pre-clinical, clinical, and research settings to overcome obstacles in sampling via traditional venipuncture. However, venipuncture remains the sampling gold standard for metabolic phenotyping of blood. This pre-sents several challenges in metabolic phenotyping workflows: accessibility for individuals in ru-ral and remote underserved areas (due to the need for trained personnel), the unamenable nature to frequent sampling protocols in longitudinal research (for its invasive nature), and sample col-lection difficulty in the young and elderly. Furthermore, venous sample stability may be compro-mised when temperate conditions necessary for cold-chain transport are beyond control. Alter-natively, research utilising microsamples extends phenotyping possibilities to inborn errors of metabolism, therapeutic drug monitoring, nutrition, as well as sport and anti-doping. Although the application of microsamples in metabolic phenotyping exists, it is still in its infancy, with whole blood being overwhelmingly the primary biofluid collected through the collection method of dried blood spots. Research into metabolic phenotyping of microsamples is limited; however, with advances in commercially available microsampling devices, common barriers such as volumetric inaccuracies and the ‘haematocrit effect’ in dried blood spot microsampling can be overcome. In this review, we provide an overview of the common uses and workflows for mi-crosampling in metabolic phenotyping research. We discuss the advancements in technologies, highlighting key considerations and remaining knowledge gaps for employment of microsamples in metabolic phenotyping research. Supporting the translation of research from the ‘bench to the community’.

Traditional applications of Interferometric Synthetic Aperture Radar (InSAR) data involved inverting an interferogram stack to determine the average displacement velocity. While this approach has useful applications in continuously deforming regions, much information is lost by simply fitting a line through the time series. Thanks to regular acquisitions across most of the the world by the ESA Sentinel-1 satellite constellation, we are now in a position to explore opportunities for near-real time deformation monitoring. In this paper we present a simple statistical approach for detecting offsets and gradient changes in InSAR time series. Our key assumption is that 5 years of Sentinel-1 data is sufficient to calculate the population standard deviation of the detection variables. Our offset detector identifies statistically significant peaks in the first, second and third difference series. The gradient change detector identifies statistically significant movements in the second derivative series. We exploit the high spatial resolution of Sentinel-1 data and the spatial continuity of geophysical deformation signals to filter out false positive detections that arise due to signal noise. When combined with near-real time processing of InSAR data these detectors, particularly the gradient change, could be used to detect incipient ground deformation associated with geophysical phenomena, for example from landslides or volcanic eruptions.

Seventy-seven percent of Irish primary school children do not meet recommended physical activity (PA) guidelines [1]. The Daily Mile (TDM) is a primary school initiative designed to increase children’s PA output. This study evaluates TDM’s perceived effect on Irish primary school children’s health-related metrics. A mixed-methods study, comprising two data collection phases, used the RE-AIM framework to evaluate TDM [2]. Phase one involved teachers, principals and classroom assistants (n = 191) from TDM-registered schools completing a questionnaire. Two TDM-registered schools participated in phase two where, (i) interviews were conducted with each principal, (ii) a teacher sub-sample (n = 4) participated in a focus group and (iii) a child sub-sample (n = 14) participated in separate focus groups. TDM was perceived to positively impact markers of children’s health, including their PA behaviour, physical fitness and social wellbeing. Inclement weather (66.5%) and a lack of time (56.5%) were reported as the top-ranked implementation barriers. Moreover, TDM’s repetitive nature often left children feeling disinterested and resulted in some teachers modifying the initiative to maintain engagement levels. Maintaining the long-term implementation of TDM and its health benefits in primary schools may require bespoke amendments to the original format to preserve children’s engagement.

The application of electrospray ionization mass spectrometry (ESI-MS) as a direct method for detecting reactive intermediates is a technique of developing importance in the routine monitoring of solution-phase reaction pathways. Here, we utilize a novel on-line photolysis ESI-MS approach to detect the photoproducts of riboflavin in aqueous solution under mildly alkaline conditions. Riboflavin is a constituent of many food products, so its breakdown processes are of wide interest. Our on-line photolysis setup allows for solution-phase photolysis to occur within a syringe using UVA LEDs, immediately prior to being introduced into the mass spectrometer via ESI. Gas-phase photofragmentation studies via laser-interfaced mass spectrometry of deprotonated riboflavin, [RFH], the dominant solution-phase species under the conditions of our study, are presented alongside the solution-phase photolysis. The results obtained illustrate the extent to which gas-phase photolysis methods can inform our understanding of the corresponding solution-phase photochemistry. We determine that the solution-phase photofragmentation observed for [RFH] closely mirrors the gas-phase photochemistry, with the m/z 241 ion being the only major condensed-phase photoproduct. Further gas-phase photoproducts are observed at m/z 255, 212, and 145. The value of exploring both the gas- and solution-phase photochemistry to characterize photochemical reactions is discussed.

The pulsatile flow rate (PFR) in the cerebral artery system and shunt ratios in bifurcated arteries are two patient-specific parameters which may affect the hemodynamic characteristics on the pathobiology of cerebral aneurysms (CAs). Accordingly, a systematic study was employed to investigate the effects of the two parameters on hemodynamic characteristics in two internal carotid artery sidewall aneurysms (i.e., ICASA-1 and ICASA-2) models. Numerical results indicate larger PFRs can cause higher WSS in some local regions of the aneurysmal dome that may increase the probability of small/secondary aneurysms generation than under smaller PFRs. The low WSS and relatively high oscillatory shear index (OSI) could appear under a smaller PFR, which has the potential to cause aneurysmal sac growth and rupture. However, the variances in PFRs and bifurcated shunt ratios have rare impacts on the time-average pressure distributions on the aneurysmal sac, although a higher PFR can contribute more to the pressure increase in ICASA-1 dome due to the relatively stronger impingement by the redirected blood stream than in ICASA-2. Simulation results also present the variances of shunt ratios have rare impacts on the hemodynamic characteristics in sacs, mainly because the bifurcated location is not close enough to the sac in present models. Furthermore, it has been found that the vortex location plays a major role in the temporal and spatial distribution of the WSS on the luminal wall, varying significantly with the cardiac period.

An open source computational fluid dynamics (CFD) solver has been incorporated into the WindNinja modeling framework widely used by wildland fire managers as well as researchers and practitioners in other fields, such as wind energy, wind erosion, and search and rescue. Here we describe incorporation of the CFD solver and evaluate its performance compared to the conservation of mass (COM) solver in WindNinja and previously published large-eddy simulations (LES) for three field campaigns conducted over isolated terrain obstacles of varying terrain complexity: Askervein Hill, Bolund Hill, and Big Southern Butte. We also compare the effects of two important model settings in the CFD solver and provide guidance on model sensitivity to these settings. Additionally, we investigate the computational mesh and difficulties regarding terrain representation. Two important findings from this work are: (1) the choice of discretization scheme for advection has a significantly larger effect on the simulated winds than the choice of turbulence model and (2) CFD solver predictions are significantly better than the COM solver predictions at windward and lee side observation locations, but no difference was found in predicted speed-up at ridgetop locations between the two solvers.

Rabies remains a significant global threat, yet accurate estimations of its impact are hindered by the lack of confirmatory diagnoses. Postmortem confirmation of rabies traditionally involves invasive brain tissue testing, a process met with resistance from deceased patients' families, impeding consent. This paper presents and evaluates an innovative yet unpublished transnasal approach for postmortem brain tissue collection, offering a minimally invasive, easier, faster, and safer method. This method preserves the cadaver's integrity, potentially easing family reluctance towards autopsies. The limited testing of both human and animal rabies in Ghana highlights the challenges in diagnosing this fatal disease. Scarce diagnostic resources and the complexity of obtaining brain tissue samples exacerbate the issue. Cultural and religious beliefs surrounding autopsies contribute to familial hesitation, viewing these procedures as disruptive and disfiguring, further complicating consent. The transnasal technique involves approaching the brain tissue through the nostrils and cribriform plate without any superficial manipulation of the patient's head and face, thereby preserving aesthetics and natural features of the person. Technological advancements and seamless One Health collaboration among governmental, non-governmental, and research entities locally and globally culminated in Ghana's first confirmed rabies diagnosis using this method of brain tissue collection. This success emphasizes the efficiency and feasibility of transnasal brain collection approach and the invaluable role of the One Health approach and collaborative efforts in overcoming diagnostic challenges in rabies control.

There is significant need for development of a new environmentally friendly, extraction-free sample collection medium that can effectively preserve and protect genetic material for point-of-care, and/or self-collection, home-collection, and mail-back testing. Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was used to create anti-ribonuclease (RNase) Deoxyribonucleic acid (DNA) aptamers against purified RNase A conjugated to paramagnetic carboxylated beads. Following 8 rounds of SELEX carried out under various stringency conditions, e.g., selection using Xtract-Free™ (XF) specimen collection medium, and elevated ambient temperature of 28 ºC, a panel of 5 aptamers was chosen following bioinformatic analysis using next-generation sequencing. The efficacy of aptamer inactivation of RNase was assessed by monitoring Ribonucleic acid (RNA) integrity by fluorometric and real-time RT-PCR analysis. Inclusion of aptamers in reaction incubations resulted in an 8,800 to 11,200-fold reduction of RNase activity, i.e., digestion of viral RNA compared to control. Thus, anti-RNase aptamers integrated into XF collection medium as well as other commercial reagents and kits have great potential for ensuring quality intact RNA for subsequent genomic analysis.

Episcopic imaging using techniques such as High Resolution Episcopic Microscopy (HREM) and its variants, allows biological samples to be visualized in three dimensions over a large field of view. Quantitative analysis of episcopic image data is undertaken using a range of methods. In this systematic review, we look at trends in quantitative analysis of episcopic images and discuss avenues for further research. Papers published between 2011 and 2022 were analyzed for details about quantitative analysis approaches, methods of image annotation and choice of image processing software. It is shown that quantitative processing is becoming more common in episcopic microscopy and that manual annotation is the predominant method of image analysis. Our meta-analysis highlights where tools and methods require further development in this field, and we discuss what this means for the future of quantitative episcopic imaging, as well as how annotation and quantification may be automated and standardized across the field.

A critical aspect of coronary heart disease (CHD) care and secondary prevention is ensuring patients have access to evidence-based information. The purpose of this review is to summarise the guiding principles, content, context and timing of information and education that is beneficial for supporting people with CHD and potential communication strategies including digital interventions. We conducted a scoping review involving searching four databases (Web of Science, PubMed, CINAHL, Medline) for articles published from January 2000 to August 2022. Literature was identified through title and abstract screening by expert reviewers. Evidence was synthesised according to the review aims. Results demonstrated that information-sharing, decision-making, goal-setting, positivity and practicality are important aspects of secondary prevention and should be patient-centred and evidenced based with consideration of patient need and preference. Initiation and duration of education is highly variable between and within people, but hence communication and support should be regular and ongoing. In conclusion, text messaging programs, smartphone applications and wearable devices are examples of digital health strategies that facilitate education and support for patients with heart disease. There is no one size fits all approach that suits all patients at all stages and hence flexibility and a suite of resources and strategies is optimal.

The PII protein is an evolutionary highly conserved regulatory protein from bacteria to higher plants. In bacteria it modulates the activity of several enzymes, transporters and regulatory factors by interacting with them and thereby regulating important metabolic hubs like carbon/nitrogen homeostasis. More than two decades ago the PII protein was characterized for the first time in plants, but its physiological role is still not sufficiently resolved. To gain more insights into the function of this protein, we investigated the interaction behaviour of AtPII with candidate proteins by BiFC and FRET/FLIM in planta and with GFP/RFP traps in vitro. In the course of these studies we found that AtPII interacts in chloroplasts with itself as well as with known interactors like NAGK in dot-like aggregates, which we named PII foci. In these novel protein aggregates AtPII interacts also with yet unknown partners, which are known to be involved in plastidic protein degradation. Further studies revealed that the C-terminal part of AtPII is crucial for the formation of PII foci. Altogether, the presented results indicate a novel mode of interaction for PII proteins with other proteins in plants, which may be a new starting point for the elucidation of physiological functions of PII proteins in plants.

Hepatic macrophages act as the liver’s first line of defense against injury. Their differentiation into pro-inflammatory or anti-inflammatory subpopulations is a critical event that maintains a delicate balance between liver injury and repair. In our investigation, we explored the influence of the small heterodimer partner (SHP), a nuclear receptor primarily associated with metabolism, on macrophage differentiation during the innate immune response. During macrophage differentiation, we observed significant alterations in Shp mRNA expression. Deletion of SHP promoted M1 differentiation while interfering with M2 polarization. Conversely, overexpression of SHP resulted in increased expression of peroxisome proliferator activated receptor gamma (Pparg), a master regulator of anti-inflammatory macrophage differentiation, thereby inhibiting M1 differentiation. Upon lipopolysaccharide (LPS) injection, there was a notable increase in the pro-inflammatory M1-like macrophages, accompanied by exacerbated infiltration of monocyte-derived macrophages (MDMs) into the livers of Shp myeloid cell specific knockout (Shp-MKO). Concurrently, we observed significant induction of tumor necrosis factor alpha (Tnfa) and chemokine (C-C motif) ligand 2 (Ccl2) expression in LPS-treated Shp-MKO livers. Additionally, the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-kB) pathways were activated in LPS-treated Shp-MKO livers. Consistently, both pathways were hindered in SHP overexpression macrophages. Finally, we demonstrated that SHP interacts with p65, thereby influencing macrophage immune repones. In summary, our study uncovered a previously unrecognized role of SHP in promoting anti-inflammatory macrophage differentiation during the innate immune response. This was achieved by SHP acting as a regulator for the Pparg, MAPK and NF-kB pathways.

Environmental DNA (eDNA) is an increasingly used non-invasive molecular tool for detecting species presence and monitoring populations. In this article, we review the current state of non-avian reptile eDNA work in aquatic systems, as well as present a field experiment on detecting the presence of painted turtle (Chrysemys picta) eDNA. Thus far, turtle and snake eDNA studies have been successful mostly in detecting the presence of these animals in field conditions. However, some instances of low detection rates and non-detection occur for these non-avian reptiles, especially for squamates. We explored this matter by sampling lentic ponds with different densities (0 kg/ha, 6 kg/ha, 9 kg/ha, and 13 kg/ha) of painted turtles over three months, attempting to detect differences in eDNA accumulation using a qPCR assay. Only one sample of the highest density pond readily amplified eDNA. Yet, estimates of eDNA concentration from pond eDNA were rank-order correlated with turtle density. We present a “shedding hypothesis”–the possibility that animals with hard, keratinized integument do not shed as much DNA as mucus-covered organisms–as a potential challenge for turtle eDNA studies. Despite challenges with eDNA inhibition and availability in water samples, we remain hopeful that eDNA can be used to detect freshwater turtles in the field. We provide key recommendations for biologists wishing to use eDNA methods for detecting non-avian reptiles.

Thoracic aortic aneurysm (TAA) has a prevalence of 0.16%-0.34% and an incidence of 7.6 per 100,000 person-years, accounting for 1%-2% of all deaths in Western countries. Currently, no effective pharmacological therapies have been identified to slow TAA development and prevent TAA rupture. Large TAAs are treated with open surgical repair and less invasive thoracic endovascular aortic repair, both of which have high perioperative mortality risk. Therefore, there is an urgent medical need to identify the cellular and molecular mechanisms underlying TAA development and rupture to develop new therapies. In this review, we summarize animal TAA models including recent developments in porcine and zebrafish models: porcine models can assess new therapeutic devices or intervention strategies in a large mammal and zebrafish models can employ large-scale small-molecule suppressor screening in microwells. The second part of the review covers current views of TAA pathogenesis, with a focus on the roles of the transforming growth factor-beta (TGFβ) pathway and the vascular smooth muscle cell (VSMC)-elastin-contractile unit. The last part discusses TAA treatment options as they emerge from recent preclinical studies.

This systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement to synthesizes the existing literature with a goal to review current conceptual frameworks of mental health of forced migrants for further practice research priorities in social work. The search was done between January 2015 to January 2021. As a result, 29 studies met inclusion criteria. Medicalizing mental health issues by relying solely on the effectiveness of medicine was a controversial risk factor that negatively affected the daily life activities of refugees and reduced their willingness for seeking professional mental health services. Empowering vulnerable minorities by giving them back their power and agency to be able to speak for themselves and raise voices of trauma and recovery was the missing protective factor for sustainable mental health practice. The benefits of group-based interventions are highlighted in which communities and individuals address mental health issues as well as isolation through building collective identities and support networks. Information and communication technologies (ICTs) can add more strength to any kind of mental health intervention. Finally, the benefits of applying ecological perspective for the mental health of refugees, and its implications for a sustainable intercultural practice are discussed. Social workers in this model are the representatives of at-risk groups, thus need more agency and creativity in reflecting client’s concrete needs.

Commonly employed methods for reversibly disrupting gene expression, such as those based on RNAi or CRISPRi, are rarely capable of achieving >80-90% downregulation, making them unsuitable for targeting genes that require more complete disruption to elicit a phenotype. Genetic deletion, on the other hand, while enabling complete disruption of target genes, often produces undesirable irreversible consequences such as cytotoxicity or cell death. Here we describe the design, development and detailed characterization of a dual-function "TRE-Lox" system for effecting either (a) doxycycline (Dox)-mediated downregulation or (b) genetic deletion of cathepsin D (CatD), based on targeted insertion of a tetracycline-response element (TRE) and two LoxP sites into the 5' end of the endogenous gene (CTSD). Using an optimized reverse-tetracycline transrepressor (rtTR) variant fused with the Krüppel-associated box (KRAB) domain, we show that CatD expression can be disrupted by as much as 98% in mouse embryonic fibroblasts (MEFs). This system is highly sensitive to Dox (IC50 = 1.46 ng/mL) and results in rapid (t1/2 = 0.57 d) and titratable downregulation of CatD. Notably, even near-total disruption of CatD expression was completely reversed by withdrawal of Dox. As expected, transient expression of Cre recombinase results in complete deletion of the CTSD gene. The dual functionality of this novel system will facilitate future studies of the involvement of CatD in various diseases, particularly those attributable to partial loss of CatD function. In addition, the TRE-Lox approach should be applicable to the regulation of other target genes requiring more complete disruption than can be achieved by traditional methods.

This study investigated the prevalence and severity of depression, anxiety, and stress and determined the association between various factors, social support, and depression and anxiety among university healthcare workers in Malaysia after the government lifted the movement control order (MCO) put in place to curb the coronavirus disease 2019 (COVID-19) pandemic. This online, cross-sectional survey recruited 399 participants from two university hospitals, and they were administered a self-reported questionnaire on demographic, personal, and clinical characteristics; COVID-19-related stressors; and coping. In addition, they completed the Multidimensional Scale of Perceived Social Support (MSPSS) to measure perceived social support, as well as the 21-item Depression, Anxiety, and Stress Scale (DASS-21) to assess depression, anxiety, and stress. We found that the prevalence of depression, anxiety, and stress were 21.8%, 31.6%, and 29.1%, respectively. Participants with moderate to extremely severe depression, anxiety, and stress made up 13.3%, 25.8%, and 8.1% of the sample, respectively. Being single or divorced, fear of frequent exposure to COVID-19 patients, those who agreed that their area of living had a high prevalence of COVID-19 cases, and uncertainty regarding the prevalence of COVID-19 cases in the area of living were associated with higher odds of depression and anxiety. Conversely, having more than three children and greater perceived friend support were associated with lower odds of depression and anxiety. The prevalence of depression, anxiety, and stress remained elevated even after the MCO was lifted.

Modification of electrode surface with a selective layer gives the possibility to detect target ana-lytes of forensic interest. 3-(4-trifluoromethyl)-phenyl)-thiophene (ThPhCF3) was deposited on a graphite (G) electrode by electrochemical oxidation and characterized as a receptor for the recognition of synthetic stimulants (2-aminoindane, buphedrone, naphyrone). First, the structural characterization of the polymeric layer were obtained from Raman spectroscopy. Second, the electrochemical profiles of selected synthetic stimulants and their affinity to ThPhCF3/G-modified electrodes were studied using square wave voltammetry and electrochemical impedance spec-troscopy. The values of the adsorption constant show the importance of – PhCF3 groups in the interaction with synthetic stimulants, namely recognition by the formation of hydrogen bonds (Kads (buphedrone) < Kads (2-AI)) and interaction with aromatic H atoms (Kads (buphedrone) < Kads (naphyrone)). It was demonstrated that the polymeric layer derived from thiophene with – PhCF3 group is capable to increase the intensity of the electrochemical signal.

Triple negative breast cancer (TNBC) is an aggressive subtype of the disease with poor clinical outcomes and limited therapeutic options. Immune checkpoint blockade (CP) has surged to the forefront of cancer therapies with widespread clinical success in a variety of cancer types. However, the percentage of TNBC patients that benefit from CP as a monotherapy is low and clinical trials have shown the need for combined therapeutic modalities. Specifically, there has been interest in combining CP therapy with radiation therapy where clinical studies primarily with external beam have suggested their therapeutic synergy, contributing to the development of anti-tumor immunity. Here, we have developed a therapeutic platform combining radionuclide therapy (RT) and immunotherapy utilizing a radiolabelled biomolecule and CP in an E0771 murine TNBC tumor model. Survival studies show that while neither monotherapy is able to improve therapeutic outcomes, the combination of RT + CP extended overall survival. Histologic analysis showed that RT + CP increased necrotic tissue within the tumor and decreased levels of F4/80+ macrophages. Flow cytometry analysis of the peripheral blood also showed that RT + CP suppressed macrophages and myeloid-derived suppressive cells, both of which actively contribute to immune escape and tumor relapse.

Proactive deprescribing is the process of stopping a medicine before harm occurs. This study aimed to specify and validate with an international sample of healthcare professionals, a proactive deprescribing process of steps and constituent activities. We developed a proactive deprescribing process framework of steps which we populated with literature-derived activities required to be undertaken by healthcare professionals. We distributed a survey to healthcare professionals in-ternationally requesting for each activity; the frequency of its occurrence in practice and whether it was important. Extended response questions invited barriers and enablers to deprescribing. The 263 survey respondents were from 25 countries. A proactive deprescribing process was developed comprising four steps: (1) Identify a patient for potential stop of a medicine, (2) Evaluate a patient for potential stop of a medicine, (3) Stop a medicine(s), (4) After a medicine has been stopped, and 17 activities. All activities were considered important by ≥70% respondents. Nine activities re-quired healthcare professionals to undertake in direct partnership with the patient and/or care-giver, of which seven were only sometimes undertaken. Deprescribing interventions should focus on addressing the barriers and enablers of healthcare professionals undertaking the activities that require direct partnership with the patient and/or caregiver.

High-fidelity patient simulation (HFPS) is widely used in professional training to enhance students’ competence in clinical management. Problem-solving (PS) and clinical reasoning (CR) skills are essential to developing students in professional competence in safe and effective care. These two skills should be initiated at the early training. However, little is known about the effects of HFPS on developing PS and CR skills in first year undergraduate students. Therefore, this pre- and post-experimental study aimed to investigate the effects of HFPS on development of PS and CR skills in first-year nursing students. The students were required to go through four sessions, preparation, pre-briefing and orientation, simulation role-playing, and debriefing, for the HFPS. The study utilized the Problem-Solving Inventory (PSI) and the Nurses Clinical Reasoning Scale (NCRS) to measure problem-solving and clinical reasoning abilities before and after HFPS. Bivariate analysis, one-sample t-test, and independent t-test were performed to evaluate the performance of the PS and CR skills at the two study periods. One hundred eighty-nine students were recruited, with a mean age of 20.56 years, and 73% were female students. The analytic results showed that the PSI, particularly in domains of Problem-Solving Confidence (PSC) (p&lt;0.001) and overall PS (p&lt;0.001), and the CR (p&lt;0.001) had significant improvement after HFPS. The study concluded that HFPS is an effective innovative method to significantly improve students’ problem-solving and clinical reasoning abilities. Nurse educators play an important role in providing explicit learning instructions in a simulation guideline that directs and guides students to learn at each stage of HFPS. Students should take more initiative and engage in their learning through HFPS to enhance their competence in knowledge and higher intellectual skills for personal and professional developments.

Farmland edge plants can support high butterfly richness. Our objective was determine if, even in farms under intensive cultivation, the diversity of plants (mostly native) in crop edges is enough to sustain a high species richness of butterfly. We characterized the vegetation on the edges of Medicago sativa farms in central Mexico and identified the species of diurnals butterflies (Rhopalocera) associated. Butterflies and plants were counted along transects at the edges of a cul-tivated field during 24 months. We found 2710 individuals of plants, belonging to 48 different species from 24 families; 1749 individuals of diurnal butterflies, belonging to 57 species from six families. Most than half of the plant species found were native flora of central Mexico and with ethnobotanical use. A similarity analysis test showed significant differences in floristic composi-tion between transects. The Canonical Correspondence Analysis between butterfly species and plant families showed three groups. Six butterfly species were migratory and four mexican en-demic species, most of them associated with a group formed by Amaranthaceae, Euphorbiaceae, Annonaceae Lamiaceae Apiaceae and Fabaceae families. The high diversity of plants in our agro-ecosystem plays an important role to sustain a high diversity of butterflies and could be useful as biological corridors.

The aim of this study was to assess the best timing to perform arthrocentesis in the management of temporomandibular disorders with regards to conservative treatment. A systematic search based on PRISMA guidelines, including a computer search with specific keywords, reference list search, and manual search was done. Relevant articles were selected after 3 search rounds for final review based on 6 predefined inclusion criteria, followed by a round of critical appraisal. Eleven publications, including 5 randomized controlled trials and 6 prospective clinical studies informed this review. The studies were divided into 3 groups based on the timing of arthrocentesis: 1). Arthrocentesis as the initial treatment, 2). Early arthrocentesis, and 3). Late arthrocentesis. Meta-analyses compared the efficacy of improvement in mouth opening and pain reduction in the 3 groups. The results were statistically significant and favoured early arthrocentesis, followed by late arthrocentesis in terms of both improvements in mouth opening and pain reduction. All 3 groups showed improvement in mouth opening and pain reduction. We conclude that early arthrocentesis may be able to produce the best clinical results, while arthrocentesis before attempting conservative treatment may produce less favourable outcomes.

Octyl methoxycinnamate (OMC) is a common UVA and UVB filter molecule that is widely used is commercial sunscreens. Here, we use gas-phase laser photodissociation spectroscopy to characterize the intrinsic photostability and photodegration products of OMC, by studying the system as its protonated form, i.e. [OMC·H]+. The major photofragments observed have, m/z 179, 161, and 133, corresponding to fragmentation on either side of the of the ether oxygen of the ester group (m/z 179, and 161) or the C-C bond adjacent to the ester carbonyl group. Additional measurements were obtained using higher-energy collisional dissociation mass spectrometry (HCD-MS), to identify fragments which result from breakdown of the vibrationally hot electronic ground state. We found that the m/z 179 and 161 ions are the main fragments produced by this route. Notably, the m/z 133 ion was not observed through HCD-MS, revealing that this product ion is only produced through a photochemical route. Our results demonstrate that UV photoexcitation of OMC is able to access a dissociative excited state surface that uniquely leads to rupture of the C-C bond adjacent to the key ester carbonyl group.

In horses, quantitative assessment of gait parameters, as the use of inertial measurement units system (IMUs), might help in the decision-making process. However, it requires financial investment, is time-consuming, and lacks accuracy if displaced. An innovative Artificial Intelligence marker-less Motion Tracking System (AI-MTS) may overcome these limitations in the field. Our aim was to compare the level of agreement and accuracy between both systems and visual clinical assessment. Twenty horses underwent locomotion analysis by visual assessment, IMUs and AI- MTS systems, in the following conditions: straight hard (SH), straight soft (SS), left and right circle hard (LCH, RCH) and soft (LCS, RCS). A greater number of horses were considered sound by clinical examination, compared to those identified as symmetric by the two gait analysis systems. More limbs were considered asymmetric by the AI-MTS compared to IMUs, suggesting its greater sensitivity. The greatest agreement between the two systems was found for the difference between two minima in vertical head position in SH, while the lowest for the difference between two minima in vertical pelvis position in SS, reflecting the difficulties in assessing asymmetry of hindlimbs. Some degree of asymmetry may be clinically relevant, suggesting its regular use in training horses.

Background: Shorter leukocyte telomere length (LTL) is observed in multiple age-related diseases, which are also associated with vitamin D deficiency (i.e., osteosarcopenia, neurocognitive disorders, cancer, osteoarthritis, etc.), which suggests a close association. In this study, we examined the relationship between vitamin D levels and LTL in older participants of the UK Biobank. Methods: Data were collected from the UK Biobank. Participants aged 60 and older (n=148,321) were included. Baseline LTL was measured using a multiplex qPCR technique and expressed as the ratio of the telomere amplification product (T) to that of a single-copy gene (S) (T/S ratio). Se-rum 25-hydroxyvitamin D (25OHD) was stratified by z score and linked to LTL in a linear regression model adjusting for covariates. Results: Compared to the medium level, a low (in the range of 16.6 nmol/L, 29.7 nmol/L) or extremely low (≤ 16.6 nmol/L) level of serum 25OHD was associated with shorter LTL: 0.018 SD (standardized β= -0.018, 95% CI -0.033 to -0.003, P=0.022) and 0.048 SD (standardized β= -0.048, 95% CI -0.083 to -0.014, P=0.006), respectively. Additionally, the high serum 25OHD groups (> 95.9 nmol/L) had 0.038 SD (standardized β= -0.038, 95% CI -0.072 to -0.004, P=0.030) shorter mean LTL than the group with medium 25OHD levels. The associations above were adjusted for multiple variables. Conclusion: In this population-based study, we identified an inverted U-shape relationship between LTL and vitamin D status. Whether high or low vitamin D-associated shorter LTL is mechanistically related to age-related conditions remains to be elucidated.

The development of microbial products for cancer treatment has been in the spotlight in recent years. In order to accelerate the lengthy and expensive drug development process, in silico screening tools are systematically employed, especially during the initial discovery phase. Moreover, considering the steadily increasing number of molecules approved by authorities for commercial use, there is a demand for faster methods to repurpose such drugs. Here we present a review on virtual screening web tools, publicly available databases of molecular targets and libraries of ligands, with the aim to facilitate the discovery of potential anticancer drugs based on microbial products. We provide an entry-level step-by-step description of the workflow for virtual screening of microbial metabolites with known protein targets, as well as two practical examples using freely available web tools. The first case presents a virtual screening study of drugs developed from microbial products using Caver Web, a web tool that performs docking along a tunnel. The second case comprises a comparative analysis between a healthy isocitrate dehydrogenase 1, a mutant that results in cancer, using the recently developed web tool PredictSNP^Onco. In summary, this review provides the basic and essential background information necessary for virtual screening experiments, which may accelerate the discovery of novel anticancer drugs.

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (Ca_Vs). Calcium entering through Ca_Vs is key for multiple neuronal processes. In this review, we will summarize recent findings that link Ca_Vs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of Ca_Vs structure, classification, function, expression and pharmacology. Next, we will summarize tools and databases to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in Ca_V genes when available. We will review pharmacological evidence of the use of Ca_V modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of Ca_Vs.

Temperature and pH can expedite the ability of pathogens to cause diseases in cold-water corals (CWCs). The present study employed a combination of histology and polymerase chain reaction diagnostic techniques to investigate potential pathogens present in the CWCs Lophelia pertusa and Madrepora oculata in the Porcupine Bank Canyon (PBC), NE Atlantic. No pathogen was observed in the Madrepora samples. Neither histology nor standard PCR detected Vibrio spp. in the corals, although using Illumina technology, V. shilonii was observed in some L. pertusa samples in low abundances (0.22%). A Rickettsiales-like organisms (RLOs) occurred at a prevalence of 8.0% and at a low infection intensity of 1 - 4. Lophelia showed a few RLOs infection from the PBC canyon head (2.7%) and high infections in the south branch (5.3%). Similarly, unidentified cells observed in L. pertusa from the south branch (4.0%) were more common than those found in the canyon head (1.3%) with a prevalence of 5.3%. Although the route of pathogen infection is unclear, a likely mode of entry could be associated with particulate availability and the feeding strategies of the scleractinian corals. This suggest that L. pertusa invests energy into an enhanced immune function and reduced susceptibility to global pathogens despite a changing ocean environment.

Pragmatic trials aim to assess intervention efficacy in usual patient care settings, contrasting with explanatory trials conducted under controlled conditions. In aging research, pragmatic trials are important designs for obtaining real-world evidence in elderly populations, which are often underrepresented in trials. In this review, we discuss statistical considerations from a frequentist approach for the design and analysis of pragmatic trials. When choosing the dependent variable, it is essential to use an outcome that is highly relevant to usual medical care while also providing sufficient statistical power. Besides traditionally used binary outcomes, ordinal outcomes can provide pragmatic answers with gains in statistical power. Cluster randomization requires careful consideration of sample size calculation and analysis methods, especially regarding missing data and outcome variables. Mixed effects models and generalized estimating equations (GEEs) are recommended for analysis to account for center effects, with tools available for sample size estimation. Multi-arm studies pose challenges in sample size calculation, requiring adjustment for design effects and consideration of multiple comparison correction methods. Secondary analyses are common but require caution due to the risk of reduced statistical power and false-discovery rates. Safety data collection methods should balance pragmatism and data quality. Overall, understanding statistical considerations is crucial for designing rigorous pragmatic trials that evaluate interventions in elderly populations under real-world conditions. In conclusion, this review focuses on various statistical topics of interest to those designing a pragmatic clinical trial, with consideration of aspects of relevance in the aging research field.

There is no doubt that seagrass beds constitute one of the most productive ecosystems in shallow coastal waters. Despite this, picoplankton in seagrass ecosystems has received relatively little attention. The purpose of this study was to compare picoplankton growth and mortality rates between seagrass and unvegetated habitats using chamber incubations. We tested two main hypotheses: (i) incubation with seagrass would result in higher bacterial growth rates due to increased DOM release from seagrass photosynthesis, and (ii) Synechococcus spp. would be lower in the presence of seagrass due to competition for inorganic nutrients. Our results showed bacterial growth rates of 2.31 and 2.44 d–1 without and with seagrass, respectively. In seagrass chambers, bacterial growth was higher than that in non-seagrass chambers, suggesting that organic carbon coming from the seagrass community may support bacterial production. Furthermore, we observed a negative Synechococcus spp. growth rate (-0.9 d–1) in the seagrass treatment, likely reflecting nutrient competition with the seagrass. Small-scale chambers proved to be a useful tool for studying the factors controlling spatial and temporal patterns of picoplankton across different habitats. Furthermore, future studies should examine picoplankton growth over a wider range of spatial scales in seagrass beds and adjacent unvegetated sediment.

PSD-95 (Dlg4) is an ionotropic glutamate receptor scaffolding protein essential in synapse stability and neurotransmission. PSD-95 levels are reduced during aging and in neurodegenerative diseases like Huntington’s disease (HD), and it is believed to contribute to synaptic dysfunction and behavioral deficits. However, the mechanism responsible for PSD-95 dysregulation under these conditions is unknown. The Heat Shock transcription Factor 1 (HSF1), canonically known for its role in protein homeostasis, is also depleted in both aging and HD. Synaptic protein levels, including PSD-95, are influenced by alterations in HSF1 levels and activity, but the direct regulatory relationship between PSD-95 and HSF1 has yet to be determined. Here, we showed that HSF1 chronic or acute depletion in cell lines and mice decreased PSD-95 expression. Furthermore, HSF1(+/-) mice had reduced PSD-95 synaptic puncta that paralleled a loss in thalamo-striatal excitatory synapses, an important circuit disrupted early in HD. We demonstrated that HSF1 binds to regulatory elements present in the PSD-95 gene and directly regulates PSD-95 expression. HSF1 DNA-binding on the PSD-95 gene was disrupted in an age-dependent manner in WT mice and worsened in HD cells and mice, leading to reduced PSD-95 levels. These results demonstrate a direct role of HSF1 in synaptic gene regulation that has important implications in synapse maintenance in basal and pathological conditions.

A Fall armyworm (FAW) is a major pest of maize and causes huge losses. Chemical control is the commonly used strategy FAW among farmers. Efficacy of baculovirus against FAW has been proven, however, farmers may not afford the products. The use of farmer produced baculovirus mixtures could provide an opportunity for a nature-based solution for FAW at low cost. This study evaluated the potential of virus extracted from FAW larvae treated with a commercial baculovirus (Littovir) for the management of FAW under laboratory and field conditions. In Laboratory, the virus extracted from 25, 50, 75 and 100 FAW larvae caused varied mortality on FAW instars. The highest mortality (45%) on 1st-3rd instars was caused by Littovir followed by virus extract from 100 FAW larvae (36%). Under field conditions, even though virus extracts did not offer adequate protection against the FAW damage, the maize yield was comparable to commercial insecticides treated plots. This study has shown the potential of use of virus extracts for management of FAW. This would offer the farmers a sustainable and affordable option for management of FAW as it would require the farmers to purchase the commercial baculovirus once and collect larvae from treated plots for repeat applications.

CC16 plays many protective roles within the lung; however, the complete biological functions, es-pecially regarding the pulmonary epithelium during infection, remain undefined. We have previ-ously shown that CC16 deficient (CC16-/-) mouse tracheal epithelial cells (MTECs) have enhanced Mp burden, compared to CC16 sufficient (WT) MTECs; therefore, in this study, we wanted to fur-ther define how the pulmonary epithelium responds to infection in the context of CC16 deficiency. Using mass spectrometry and quantitative proteomics to analyze proteins secreted apically from MTECs grown at an air-liquid interface, we investigated the protective effects that CC16 elicits within the pulmonary epithelium during Mycoplasma pneumoniae (Mp) infection. When chal-lenged with Mp, WT MTECs have an overall reduction in apical protein secretion, whereas CC16-/- MTECs have increased apical protein secretion compared to their unchallenged controls. Fol-lowing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) assessment, many of the proteins upregulated from CC16-/- MTECS (unchallenged and during Mp infection) were related to airway remodeling, which were not observed by WT MTECs. These findings sug-gest that CC16 is instrumental in providing protection within the pulmonary epithelium during respiratory infection with Mp, the major causative agent of community-acquired pneumoniae.

Fire detection from satellite sensors relies on an accurate estimation of the unperturbed state of a target pixel, from which an anomaly can be isolated. Methods for estimating the radiation budget of a pixel without fire depend upon training data derived from the location's recent history of brightness temperature variation over the diurnal cycle, which can be vulnerable to cloud contamination and the effects of weather. This study proposes a new method that utilises the common solar budget found at a given latitude in conjunction with an area's local solar time to aggregate a broad-area training dataset, which can be used to model the expected diurnal temperature cycle of a location. This training data is then used in a temperature fitting process with the measured brightness temperatures in a pixel, and compared to pixel-derived training data and contextual methods of background temperature determination. Results of this study show similar accuracy between clear-sky medium wave infrared upwelling radiation and the diurnal temperature cycle estimation compared to previous methods, with demonstrable improvements in processing time and training data availability. This method can be used in conjunction with brightness temperature thresholds to provide a baseline for upwelling radiation, from which positive thermal anomalies such as fire can be isolated.

Insulin receptors are internalized by endothelial cells; however, the impact of hyperinsulinemia on this process is not known. Thus, the aim of this study is to determine the role of hyperinsulinemia on insulin receptor function and internalization, as well as the potential impact of protein tyrosine phosphatase 1B (PTP1B). To this end, hippocampal microvessels were isolated from male C57Bl/6J mice on either a control or high-fat diet and assessed for insulin receptor signaling. Cell surface insulin receptors in brain microvascular endothelial cells were labelled with biotin to assess the role hyperinsulinemia plays on receptor internalization in response to stimulation, with and without Claramine treatment, a potent PTP1B antagonist. Our results indicated that insulin receptor levels increased in tandem with insulin receptor dysfunction in the high-fat diet mouse hippocampal microvessels. Hyperinsulinemic cell-receptors demonstrate a shift in splice variation towards decreased IR-A/IR-B ratios and demonstrate a higher membrane-localized proportion. This corresponded with decreased autophosphorylation at sites critical for receptor internalization and signaling, however, Claramine restored signaling and receptor internalization in hyperinsulinemic cells. In conclusion, hyperinsulinemia negatively impacts brain microvascular endothelial cell insulin receptor function and internalization, likely through both alternative splicing and increased negative feedback from PTP1B.

Lamb waves occur in thin-walled structures in two wave modes, the symmetric and antisymmetric mode. Their oscillation on the structures‘ surfaces is either in phase (symmetric) or shifted by a phase angle of π (antisymmetric). In this work, a method is developed to compare the surfaces‘ oscillation phase relation. It is based on the evaluation of time signals regarding the instantaneous phase angle using the continuous wavelet transformation and as a comparative method the short-time Fourier transformation. For this purpose, numerical simulations utilizing the finite element method provide time signals from the top and bottom surface of different thin-walled structures. They differ with respect to their material settings and laminate configurations. The numerically obtained time signals are evaluated by the developed methods. The occurring oscillation phase differences on the top and bottom surface are studied and both methods are compared. Subsequently, the oscillation phase is evaluated experimentally for the wave propagation in a fiber metal laminate. It is shown that the method based on the continuous wavelet transformation is suitable for the evaluation of oscillation phase relations in time signals. Additionally, it is proven that fiber metal laminates show only two phase relations which indicates the occurrence of Lamb waves.

Insecticides with novel modes of action are required to complement the pyrethroids currently relied upon for controlling malaria vectors. One example of this is the neonicotinoid clothianidin, which is found in SumiShield™ 50WG used in indoor residual spraying (IRS). In a preliminary experiment, mortality in insecticide susceptible and resistant An. gambiae adults exposed to SumiShield™ 50WG-treated filter papers reached 80% by 3-days post-exposure and 100% by 6-days post-exposure. Next, cement, wood, and mud tiles were treated with SumiShield™ 50WG or K-Othrine® WG250 (deltamethrin IRS formulation) and insecticide resistant and susceptible Anopheles and Aedes were exposed to these surfaces periodically for up to 18-months. Pyrethroid resistant Cx. quinquefasciatus were also exposed at 9 months. Between exposures tiles were stored in heat and relative humidity conditions reflecting those found in the field. On these surfaces, SumiShield™ 50WG was effective at killing both susceptible and resistant An. gambiae for 18 months post-treatment, while mortality amongst the resistant strains when exposed to deltamethrin (K-Othrine® WG250) IRS was not above that of the negative control. Greater efficacy of SumiShield™ 50WG was also demonstrated against insecticide resistant strains of An. funestus compared to deltamethrin, though the potency was lower when compared with An. gambiae. In general, a higher efficacy of SumiShield™ 50WG was observed on cement and mud compared to wood. SumiShield™ 50WG demonstrated poor residual activity against Aedes aegypti and Culex quinquefasciatus. Overall, the results suggest SumiShield™ 50WG is well suited for malaria control.

The majority of urban inhabitants in low- and middle-income country (LMIC) cities live in deprived urban areas. However, statistics and data (e.g., local monitoring of Sustainable Development Goals - SDGs) are hindered by the unavailability of spatial data at metropolitan, city and sub-city scales. Deprivation is a complex and multidimensional concept, which has been captured in existing literature with a strong focus on household-level deprivation while giving limited attention to area-level deprivation. Within this scoping review, we build on existing literature on household- as well as area-level deprivation frameworks to arrive at a combined understanding of how urban deprivation is defined with a focus on LMIC cities. The scoping review was enriched with local stakeholder workshops in LMIC cities to arrive at our framework of Domains of Deprivations, splitting deprivation into three different scales and nine domains. (1) Socio-Economic Status and (2) Housing Domains (Household scale); (3) Social Hazards & Assets, (4) Physical Hazards & Assets, (5) Unplanned Urbanization and (6) Contamination (Within Area scale); and (7) Infrastructure, (8) Facilities & Services and (9) city Governance (Area Connect scale). The Domains of Deprivation framework provides a clear guidance for collecting data on various aspects of deprivation, while providing the flexibility to decide at city level which indicators are most relevant to explain individual domains. The framework provides a conceptual and operational base for the Integrated Deprived Area Mapping System (IDEAMAPS) Project for the creation of a data ecosystem, which facilitates the production of routine, accurate maps of deprived “slum” areas at scale across cities in LMICs. The Domains of Deprivation Framework is designed to support diverse health, poverty, and development initiatives globally to characterize and address deprivation in LMIC cities.

The advanced industrial systems are characterized by complex event-driven processes. The specification and computer analysis are illustrated by the common problem of a servo drive with the PWM controller. A mathematical model from the class of Cauchy problems with non-liner control logic is presented to resolve the task discussed. The designed model is performed in two stages: the mathematical model specification (modeling) and implementation (simulation). Two approaches to make a model specification are considered, the first one is the traditional structural technique, and the advanced method is based on the finite state machine paradigm. Structural and finite state software models are built in progressive simulation tools. Computer implementation of the software models of hybrid systems is performed using platform built-in libraries with numerical methods and algorithms for correct event detection. The results of computational experiments for transient processes of phase variables are qualitatively identical, that proves the adequacy of the developed models. The algorithm for asymptotic event detection is considered in detail. This technique demonstrated the best results by the one-sidedness criterion, which is explained by using the author’s algorithm for the integration step determining and the event function dynamics monitoring in the vicinity of the event limits.

Interferons (IFNs) are cytokines involved in the immune response that act on innate and adaptive immunity. These proteins are natural cell-signaling glycoproteins expressed in response to viral infections, tumors, and biological inducers and constitute the first line of defense of vertebrates against infectious agents. They have been marketed for more than 30 years with considerable impact on the global therapeutic protein market thanks to their diversity in terms of biological activities. They have been used as single agents or with combination treatment regimens, demonstrating promising clinical results, resulting in 22 different formulations approved by regulatory agencies. The 163 clinical trials with currently active IFNs reinforce their importance as therapeutics for human health. However, their application has presented difficulties due to the molecules’ size, sensitivity to degradation, and rapid elimination from the bloodstream. For some years now, work has been underway to obtain new drug delivery systems to provide adequate therapeutic concentrations for these cytokines, decrease their toxicity and prolong their half-life in the circulation. Although different research groups have presented various formulations that encapsulate IFNs, to date, there is no formulation approved for use in humans. The current review exhibits an updated summary of all encapsulation forms presented in the scientific literature for these cytokines IFNα, IFNß, and IFNγ, from the year 1996 to the year 2021, considering parameters such as: encapsulating matrix, route of administration, and encapsulation.

This paper focuses on parametric model order reduction (PMOR) of guided ultrasonic wave propagation and its interaction with damage in a fiber metal laminate (FML). Structural health monitoring in FML seeks to detect, localize and characterize the damage with high accuracy and minimal use of sensors. This can be achieved by the inverse problem analysis approach which employs the signal measurement data recorded by the embedded sensors in the structure. The inverse analysis requires to solve the forward simulation of the underlying system several thousand times. These simulations are often exorbitantly expensive and triggered the need for improving their computational efficiency. A PMOR approach hinged on the proper orthogonal decomposition method is presented in this paper. An adaptive parameter sampling technique is established with the aid of a surrogate model to efficiently update the reduced-order basis in a greedy fashion. A numerical experiment is conducted to illustrate the parametric training of the reduced-order model. The results show that the reduced-order solution based on the PMOR approach is accurately complying with that of the high fidelity solution.

C-peptide is used as a measure of endogenous insulin production. Given that insulin and C-peptide are produced in equal amounts, C-peptide is typically used to differentiate between external and endogenously produced insulin in insulin-treated type 1 diabetes mellitus (T1DM). In a clinical setting, a decline in C-peptide is regarded as a loss of beta cell function. However, physiological conditions may also be associated with low C-peptide levels. The authors of this paper use a low-carbohydrate diet, the so-called paleolithic ketogenic diet (PKD), in the treatment of various conditions and observed that C-peptide is typically low on this diet. In order to characterize C-peptide levels on this diet, we designed a study to retrospectively assess C-peptide levels in 100 non-T1DM subjects. We found that 55% of the subjects had a C-peptide level below the standard reference range. C-peptide levels correlated with glucose levels. A significant correlation was found between C-peptide and age, with younger subjects having lower C-peptide levels. Males also showed lower C-peptide levels than females. Given the increasing number of patients using low-carbohydrate diets worldwide, physicians should be aware of laboratory correlates of low-carbohydrate diets, including low C-peptide levels, most importantly to prevent incorrect T1DM diagnosis.

Powered ankle prostheses have been proven to improve the walking economy of people with transtibial amputation. All commercial powered ankle prostheses that are currently available can only perform one-degree-of-freedom motion in a limited range. However, studies have shown that the frontal plane motion during ambulation is associated with balancing. In addition, as more advanced neural interfaces have become available for people with amputation, it is possible to fully recover ankle function by combining neural signals and a robotic ankle. Accordingly, there is a need for a powered ankle prosthesis that can have active control on not only plantarflexion and dorsiflexion but also eversion and inversion. We designed, built, and evaluated a two-degree-of-freedom (2-DoF) powered ankle-foot prosthesis that is untethered and can support level-ground walking. Benchtop tests were conducted to characterize the dynamics of the system. Walking trials were performed with a 77 kg subject that has unilateral transtibial amputation to evaluate system performance under realistic conditions. Benchtop tests demonstrated a step response rise time of less than 50 milliseconds for a torque of 40 N·m on each actuator. The closed-loop torque bandwidth of the actuator is 9.74 Hz. Walking trials demonstrated torque tracking errors (root mean square) of less than 7 N·m. These results suggested that the device can perform adequate torque control and support level-ground walking. This prosthesis can serve as a platform for studying biomechanics related to balance and has the possibility of further recovering the biological function of the ankle-subtalar-foot complex beyond the existing powered ankles.

Herein, we report on a giant thermoelectric figure of merit of a non-degenerate fluorine-doped single-walled carbon nanotube (FSWCNT) using a tractable analytical approach and the phonon lattice Boltzmann model (LBM). We investigate the influence of the doping concentration, and the overlapping integrals on the ZT. The ZT and the temperature range of operation can be tuned using the doping (impurity) concentration and the overlapping integrals, respectively. The lattice thermal conductivity obtained using the phonon LBM was calculated to be 107.2 W/mK which yielded a ZT greater than 20. Interestingly, the ZT obtained is higher than what has been reported in superlattices, (ZT~1.4) and superlattice nanowire, (ZT~ 4) at 300 K, making FSWCNT a potential candidate for thermoelectric applications.

Trichoderma has been widely studied for its potential as a biocontrol agent against plant pathogenic organisms. Trichoderma's biological control mechanisms include competition, modification of environmental conditions, antibiosis, induction of plant defensive mechanisms, and mycoparasitism. Trichoderma species are known to produce a variety of secondary metabolites that have antifungal activity. These metabolites include peptaibols, gliotoxin, and trichokonins. Trichoderma also produces chitinases and β-1,3-glucanases that can degrade the cell walls of fungal pathogens. In addition to direct antagonism against fungal pathogens, Trichoderma can also induce systemic or localised resistance in plants, which is achieved through the production of elicitors such as chitin oligosaccharides and β-glucans that activate plant defence responses. Trichoderma can also form mutualistic associations with plants. In these associations, Trichoderma colonises the roots of plants and promotes plant growth by increasing nutrient uptake and inducing systemic resistance. Using Trichoderma as a biocontrol agent has several advantages over conventional crop protection techniques based on applying synthetic pesticides.

The genus Dirphys Howard is synonymized with Encarsia Förster syn. n. and treated as a species-group of Encarsia, referred to henceforth as the Encarsia mexicana species-group. The monophyly of Encarsia is discussed in relation to Dirphys. The new synonymy is based on phylogenetic analyses of the nuclear ribosomal 28S-D2 gene region (43 taxa, 510 bp). The Encarsia mexicana species-group is recovered as strongly monophyletic within Encarsia. All species of the Encarsia mexicana species-group are revised. The group includes six previously described species, and fourteen newly described species. All species are described (or redescribed) and illustrated. Detailed distributional data, and, where available, plant associate and host records are provided for all species. Encarsia myartsevae Kresslein &amp; Polaszek nom. nov. is here proposed as a replacement name for Encarsia mexicana Myartseva, now preoccupied by Encarsia mexicana (Howard). A dichotomous identification key, supplemented by an online multiple-entry key, is provided for all species.

Differential RNA editing by adenosine deaminases that act on RNA (ADARs) has been implicat-ed in several neurological disorders, including Parkinson’s disease (PD). Here, we report results of an RNAi screen of genes differentially regulated in adr-2 mutants, normally encoding the only catalytically active ADAR in Caenorhabditis elegans, ADR-2. Subsequent analysis of candidate genes that alter the misfolding of human α-synuclein (α-syn) and dopaminergic neurodegenera-tion, two PD pathologies, reveal that reduced expression of xdh-1, the ortholog of human xanthine dehydrogenase (XDH), is protective against α-synuclein-induced dopaminergic neurodegenera-tion. Further RNAi experiments show that WHT-2, the worm ortholog of the human ABCG2 transporter and a predicted interactor of XDH-1, is the rate-limiting factor in the ADR-2, XDH-1, WHT-2 system for dopaminergic neuroprotection. Proteomic analysis indicates that the editing of one nucleotide in wht-2 RNA leads to the substitution of threonine with alanine at residue 124 in the WHT-2 protein, changing its structure. Thus, we propose a model where wht-2, is edited by ADR-2 which promotes optimal export of uric acid, a known substrate of WHT-2 and a product of XDH-1 activity. In the absence of editing, uric acid export is limited provoking a reduction in xdh-1 transcription to limit uric acid production and maintain cellular homeostasis. In turn, ele-vation of uric acid is protective against dopaminergic neuronal cell death. These data indicate that modifying specific targets of RNA editing may represent a promising therapeutic strategy for PD.

Hallyu or the Korean wave has sweeped through nations especially the Philippines. This exploratory study offers a dip into the effects of the Hallyu wave on a Filipino speaker through ambient exposure, consequently on the development of a Korean proto-lexicon through indirect vocabulary acquisition. Finally, a focus group discussion and a preliminary assessment tested out the waters of the effects of Hallyu on casual Filipino speakers. A thorough statistically comprehensive qualitative study on the acquisition framework is recommended to provide substantial evidence to support the framework.

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses metabolic dysfunction-associated fatty liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH), with MASH posing a risk of progression to cirrhosis and hepatocellular carcinoma (HCC). The global prevalence of MASLD is estimated at approximately a quarter of the population, with significant healthcare costs and implications for liver transplantation. The pathogenesis of MASLD involves intrahepatic liver cells, extrahepatic components, and immunological aspects, particularly the involvement of macrophages. Hepatic macrophages are a crucial cellular component of the liver and play vital roles in liver function, contributing significantly to tissue homeostasis and swift responses during pathophysiological conditions. Recent advancements in technology have revealed the remarkable heterogeneity and plasticity of hepatic macrophage populations and their activation states in MASLD, challenging traditional classification methods like the M1/M2 paradigm and highlighting the coexistence of harmful and beneficial macrophage phenotypes that are dynamically regulated during MASLD progression. This complexity underscores the importance of considering macrophage heterogeneity in therapeutic targeting strategies, including their distinct ontogeny and functional phenotypes. This review provides an overview of macrophage involvement in MASLD progression, combining traditional paradigms with recent insights from single-cell analysis and spatial dynamics. It also addresses unresolved questions and potential therapeutic targets in this area.

Guided ultrasonic waves are suitable for use in the context of structural health monitoring of thin-walled, plate-like structures. Hence, observing the wave propagation in the plates can provide an indication of whether damage has occurred in the structure. In this work, the wave propagation in fiber metal laminate consisting of thin steel foils and layers of carbon fiber-reinforced polymer is studied, focusing on the main propagation characteristics like dispersion diagrams and displacement fields. For this purpose, the dispersion diagrams derived from the analytical framework and numerical simulations are first determined and compared to each other. Next, the displacement fields are computed using the global matrix method for two excitation frequencies. The results derived from the analytical framework is used to validate numerically determined displacement fields based on a 2D and a 3D modeling approach. For both investigations the results of the analytical treatment and the numerical simulation show good agreement. Furthermore, the displacement field reveals the typical and well-known characteristics of the propagation of guided waves in thin-walled structures. Since the use of full 3D models involves a very high computational cost, this work also successfully investigates the possibility for model order reduction to decrease the computational time and costs of the simulation without the loss of accuracy.

Marburg virus (MARV) is a lipid-enveloped negative sense single stranded RNA virus, which can cause a deadly hemorrhagic fever. MARV encodes seven proteins, including VP40 (mVP40), a matrix protein that interacts with the cytoplasmic leaflet of the host cell plasma membrane. VP40 traffics to the plasma membrane inner leaflet, where it assembles to facilitate the budding of viral particles. VP40 is a multifunctional protein that interacts with several host proteins and lipids to complete the viral replication cycle, but many of these host-interactions remain unknown or are poorly characterized. In this study, we investigated the role of a hydrophobic loop region in the carboxy-terminal domain (CTD) of mVP40 that shares sequence similarity with the CTD of Ebola virus VP40 (eVP40). These conserved hydrophobic residues in eVP40 have been previously shown to be critical to plasma membrane localization and membrane insertion. An array of cellular experiments and confirmatory in vitro work strongly suggests proper orientation and hydrophobic residues (Phe281, Leu283, and Phe286) in the mVP40 CTD are critical to plasma membrane localization. In line with the different functions proposed for eVP40 and mVP40 CTD hydrophobic residues, molecular dynamics simulations demonstrate large flexibility of residues in the EBOV CTD whereas conserved mVP40 hydrophobic residues are more restricted in their flexibility. This study sheds further light on important amino acids and structural features in mVP40 required for its plasma membrane localization as well as differences in the functional role of CTD amino acids in eVP40 and mVP40.

The bacterium Yersinia ruckeri causes enteric redmouth disease in salmonids and hence has substantial economic implications for the farmed fish industry. The Norwegian Y. ruckeri outbreak isolate NVH_3758 carries a relatively uncharacterized plasmid, pYR4, which encodes both type 4 pili and a type 4 secretion system. In this study, we demonstrate that pYR4 does not impose a growth burden on the Y. ruckeri host bacterium, nor does the plasmid contribute to twitching motility (an indicator of type 4 pilus function) or virulence in a Galleria mellonella larval model of infection. However, we show that pYR4 is conjugative. We also reveal, through mutagenesis, that pYR4 encodes a functional post-segregational killing system, HigBA, that is responsible for plasmid maintenance within Y. ruckeri. This is the first toxin-antitoxin system to be characterized for this organism. Whilst further work is needed to elucidate the virulence role of pYR4 and whether it contributes to bacterial disease under non-laboratory conditions, our results suggest that the plasmid possesses substantial stability and transfer mechanisms that imply importance within the organism. These results add to our understanding of the mobile genetic elements and evolutionary trajectory of Y. ruckeri as an important commercial pathogen, with consequences for human food production.

Background: We previously developed a refined, tumor selective adenovirus, Ad5NULL-A20, har-boring tropism ablating mutations in each major capsid protein, to ablate all native means of infection. We incorporated a 20mer peptide (A20) in the fiber knob for selective infection via αvβ6 integrin, a marker of aggressive epithelial cancers. Methods: To ascertain the selectivity of Ad5NULL-A20 for αvβ6 positive tumor cell lines of pancreatic and breast cancer origin, we performed reporter gene and cell viability assays. Biodistribution of viral vectors in mice harboring xenografts with low, medium, and high αvβ6 levels was quantified by qPCR for viral genomes 48 hours post intravenous administration. Results: Ad5NULL-A20 vector transduced cells in an αvβ6 selective manner, whilst cell killing me-diated by oncolytic Ad5NULL-A20 was αvβ6 selective. Biodistribution analysis following intrave-nous administration into mice bearing breast cancer xenografts demonstrated that Ad5NULL-A20 resulted in significantly reduced liver accumulation coupled with increased tumor accumulation compared to Ad5 in all three models, with tumor: liver ratios improved as a function of αvβ6 expression. Conclusions: Ad5NULL-A20 based virotherapies efficiently target αvβ6 integrin positive tumors following intravenous administration, validating the potential of Ad5NULL-A20 for systemic ap-plications, enabling tumor selective overexpression of virally encoded therapeutic transgenes.

The recent detection of SARS-CoV-2 RNA in feces has led to speculation that it can be transmitted via the fecal-oral/ocular route. This review aims to critically evaluate the incidence of gastrointestinal (GI) symptoms, the quantity and infectivity of SARS-CoV-2 in feces and urine, and whether these pose an infection risk in sanitary settings, sewage networks, wastewater treatment plants, and the wider environment (e.g. rivers, lakes and marine waters). Overall, severe GI dysfunction is only evident in a small number of COVID-19 cases, with 11 ± 2% exhibiting diarrhea and 12 ± 3% exhibiting vomiting and nausea. In addition to these cases, SARS-CoV-2 RNA can be detected in feces from some asymptomatic, mildly- and pre-symptomatic individuals. Fecal shedding of the virus peaks in the symptomatic period and can persist for several weeks, but with declining abundances in the post-symptomatic phase. SARS-CoV-2 RNA is occasionally detected in urine, but reports in fecal samples are more frequent. The abundance of the virus genetic material in both urine (ca. 10²-10⁵ gc/ml) and feces (ca. 10²-10⁷ gc/ml) is much lower than in nasopharyngeal fluids (ca. 10⁵-10¹¹ gc/ml). There is strong evidence of multiplication of SARS-CoV-2 in the GI tract and infectious virus has occasionally been recovered from both urine and stool samples. The level and infectious capability of SARS-CoV-2 in vomit remain unknown. In comparison to enteric viruses transmitted via the fecal-oral route (e.g. norovirus, adenovirus), the likelihood of SARS-CoV-2 being transmitted via feces or urine appears lower due to the lower relative amounts of virus present in feces/urine. The biggest risk of transmission will occur in clinical and care home settings where secondary handling of people and urine/fecal matter occurs. In addition, while SARS-CoV-2 RNA genetic material can be detected by in wastewater, this signal is greatly reduced by conventional treatment. Our analysis also suggests the likelihood of infection due to contact with sewage-contaminated water (e.g. swimming, surfing, angling) or food (e.g. salads, shellfish) is extremely low or negligible based on very low predicted abundances and limited environmental survival of SARS-CoV-2. These conclusions are corroborated by the fact that over eight million global cases of COVID-19 have occurred, but exposure to feces or wastewater has never been implicated as a transmission vector.

Heat shock factor 1 (HSF1) is a transcription factor crucial for regulating heat shock response (HSR), one of the significant cellular protective mechanisms. When cells are exposed to proteotoxic stress, HSF1 induces the expression of heat shock proteins (HSPs) to act as chaperones, correcting the protein-folding process and maintaining proteostasis. In addition to its role in HSR, HSF1 is overexpressed in multiple cancer cells, where its activation promotes malignancy and leads to poor prognosis. The mechanisms of HSF1-induced tumorigenesis are complex and involve diverse signaling pathways, dependent on cancer type. With its important roles in tumorigenesis and tumor progression, targeting HSF1 offers a novel cancer treatment strategy. In this article, we examine the basic function of HSF1 and its regulatory mechanisms, focus on the mechanisms involved in HSF1’s roles in different cancer types, and examine current HSF1 inhibitors as novel therapeutics to treat cancers.

Background: Although previous studies have implicated a role for the stool microbiome in cancer cachexia, the fecal microbiome has not been previously characterized for patients with pancreatic ductal adenocarcinoma (PDAC) and cachexia treated with nutritional interventions such as enteral feeding. Methods: The PANCAX-1 (NCT02400398) prospective trial enrolled 31 cachectic advanced PDAC patients to receive jejunal tube peptide-based diet for 12 weeks who were planned for palliative chemotherapy. Out of 16 evaluable patients, 62.5% receiving enteral feeding met the primary endpoint of weight stability at 12 weeks. As part of an exploratory analysis of the PANCAX-1 trial, serial stool and blood samples were collected at 0 (C1D1), 6 (C2D1), and 12 (C3D1) weeks over the 12-week period of enteral feeding. Stool samples were analyzed using 16S v4 sequencing of the microbiome. Up to 219 plasma metabolites were analyzed by mass spectrometry and high-performance liquid chromatography. Results: A total of 29 stool samples were prospectively collected from 16 subjects with PDAC enrolled in PANCAX-1 who were evaluable for weight stability. Over 12 weeks of enteral feeding, statistically significant increases in the abundance of bacterial genera such as Veillonella (p=0.0150) and Actinomyces (p=0.0390) were observed, while there was a lower abundance of Bacteroides (p=0.0150) and Butyricicoccus (p=0.0390). Greater abundance of Veillonella and reduced Bifidobacterium at baseline were linked to greater weight stability. Plasma metabolomics in 10 subjects showed that weight unstable patients had significantly decreased levels of essential (L-histidine, L-phenylalanine) and non-essential amino acids (L-citrulline, L-tyrosine, all p<0.05) at the end of 12 weeks of enteral feeding. High stool Veillonella abundance was significantly associated with increases in the nucleotide 2-deoxycytidine 5-diphosphate and essential amino acid L-isoleucine but decreased TCA cycle metabolite alpha-ketoglutarate (all p<0.05). Conclusions: We are the first to demonstrate the feasibility of stool microbiome profiling and plasma metabolomics in paired stool and plasma samples from a prospective cohort of advanced PDAC patients on enteral feeding as their primary source of nutrition. Our findings are hypothesis-generating in that metabolites unique to weight stability and abundance of stool bacterial genera may inform future studies of anti-cachexia therapies involving enteral feeding or microbial modulation.

Dengue (DENV) and Zika (ZIKV) virus continue to pose significant challenges globally due to their widespread prevalence and severe health implications. Given the absence of effective vaccines and specific therapeutics, targeting of the highly conserved NS5 RNA-dependent RNA polymerase (RdRp) domain has emerged as a promising strategy. However, limited efforts have been made to develop inhibitors for this crucial target. In this study, we employed an integrated in silico approach utilizing combinatorial chemistry, docking, molecular dynamics simulations, MM/GBSA, and ADMET studies to target the allosteric N-pocket of DENV3-RdRp and ZIKV-RdRp. Using this methodology, we designed lycorine analogs with natural S-enantiomers (LYCS) and R-enantiomers (LYCR) as potential inhibitors of non-structural protein 5 (NS5) in DENV3 and ZIKV. Notably, 12 lycorine analogs displayed a robust binding free energy (&lt;-9.00 kcal/mol), surpassing that of RdRp-Ribavirin (&lt;-7.00 kcal/mol) along with promising ADMET score predictions (&lt;4.00), of which (LYCR728-210, LYCS728-210, LYCR728-212, LYCS505-214) displayed binding properties to both DENV3 and ZIKV targets. This study highlights the potential of non-nucleoside lycorine-based analogs with different enantiomers that may present different or even completely opposite metabolic, toxicological, and pharmacological profiles as promising candidates for inhibiting NS5-RdRp in ZIKV and DENV3, paving the way for further exploration for the development of effective antiviral agents.

The human adenovirus phylogenetic tree is split across seven species (A-G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of preexisting immunity detected across screened populations. However, many aspects of the basic virology of species D, such as their cellular tropism, receptor usage and in vivo biodistribution profile, remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49), a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen whilst avoiding liver interactions, such as intravascular vaccine applications.

Following ischemic stroke, the degradation of myelin and other cellular membranes surpasses the lipid-processing capabilities of resident microglia and infiltrating macrophages. This imbalance leads to foam cell formation in the infarct and areas of secondary neurodegeneration, instigating sustained inflammation and furthering neurological damage. Given that mitochondria are the primary sites of fatty acid metabolism, augmenting mitochondrial biogenesis (MB) may enhance lipid processing, curtailing foam cell formation and post-stroke chronic inflammation. Previous studies have shown that the pharmacological activation of the β2-adrenergic receptor (β2-AR) stimulates MB. Consequently, our study sought to discern the effects of intensified β2-AR signal-ing on MB, the processing of brain lipid debris, and neurological outcome using a mouse stroke model. To achieve this goal, aged mice were treated with formoterol, a long-acting β2-AR ago-nist, daily for two and eight weeks following stroke. Formoterol increased MB in the infarct re-gion, modified fatty acid metabolism, and reduced foam cell formation. However, it did not re-duce markers of post-stroke neurodegeneration or improve recovery. Our findings suggest that boosting MB in myeloid cells is one component of a therapeutic avenue for improving brain lipid debris processing after stroke.

This work investigates how integrated polyimide inlays with applied sensor bodies influence the guided ultrasonic wave propagation in narrow glass fiber-reinforced polymer specimens. Preliminary numerical simulations indicate that in a damping-free specimen, the inlays show reflections for the S0-mode propagation. Hence, an air-coupled ultrasonic technique and a 3D laser Doppler vibrometer measurement are used to measure different parts of the propagating waves’ displacement field after burst excitation at different frequencies. No significant reflections on the inlay can be seen in the experiments. However, it is shown that the reflections from the strip specimen’s narrow width cause periodical reflections that superimpose with the excited wave fronts. A continuous wavelet transformation in the time-frequency domain filters discontinuities from the measurement signal and is used for reconstruction of the time signals. The reconstructed signals are used in a spatial continuous wavelet transformation to identify the occurring wavelengths and hence to prove the assumption of reflections from the narrow edges. Since the amplitude of the reflections identified in the numerical data at the polyimide inlays are an order of magnitude smaller than the excited wave packages, it is concluded that material damping of the epoxy resin matrix extincts possible reflections from the inlays.

(1) Background: When the Omicron variant of SARS-CoV-2 first emerged in Germany in January 2022, data on related disease severity among children and adolescents was not yet available. Given Omicron’s high transmissibility, the ability to assess its impact on admission and hospitalization rates in children’s hospitals is critical for the purpose of understanding the scope of its burden on the German health care system. (2) Methods: From January 24, 2022 to July 31, 2022, SARS-CoV-2 cases admitted to German pediatric hospitals were monitored via a national, clinician-led reporting system (CLRS) established by the German Society for Pediatric Infectious Diseases (DGPI). Cases treated on general wards and intensive care units, as well as patient age and need for respiratory support were recorded. (3) Results: From January to July 2022, a median of 1.7 cases (range 0.4–3) per reporting pediatric hospital per day were hospitalized on general wards, whereas a median of 0.1 cases (range 0–0.4 cases) were on intensive care units. Of all hospitalized patients, 4.2% received respiratory support. (4) Conclusions: Despite the high incidence rates documented in connection with the Omicron variant in early 2022, the number of pediatric hospital admissions, and especially the number of cases with need for intensive care treatment and respiratory support due to a symptomatic SARS-CoV-2 infection, remained relatively low. Higher Omicron incidence rates had only a modest impact on SARS-CoV-2-related admissions and hospitalization in German children’s hospitals.

Sonoran felids are threatened by drought and habitat fragmentation. Vector range expansion and anthropogenic factors such as habitat encroachment and climate change are altering viral evolutionary dynamics and exposure. However, little is known about the diversity of viruses present in these populations. Small felid populations with lower genetic diversity are likely to be most threatened with extinction by emerging diseases, as with other selective pressures, due to having less adaptive potential. We used a metagenomic approach to identify novel circoviruses, which may have a negative impact on the population viability, from confirmed bobcat (Lynx rufus) and puma (Puma concolor) scats collected in Sonora, Mexico. Given some circoviruses are known to cause disease in their hosts, such as porcine and avian circoviruses, we took a non-invasive approach using scat to identify circoviruses in free-roaming bobcats and puma. Three circovirus genomes were determined, and, based on the current species demarcation, they represent two novel species. Phylogenetic analyses reveal that one circovirus species is more closely related to rodent associated circoviruses and the other to bat associated circoviruses, sharing the highest genome-wide pairwise identity of approximately 70% and 63%, respectively. At this time, it is unknown whether these scat-derived circoviruses infect felids, their prey, or another organism that might have had contact with the scat in the environment. Further studies should be conducted to elucidate the host of these viruses and assess health impacts in felids.

The young adolescents’ sexual behaviors are under-investigated. In this quantitative descriptive study, we examined the 2019 Middle School Youth Risk Behavior Survey data of 66,366 young adolescents ages 10-14 from 10 states to determine the prevalence of early sexual debut among young adolescents. Complex sampling design was used to produce descriptive statistics and cross-tabulations to describe young adolescents' sexual behaviors. Early sexual debut was reported at nearly 8%, and 4% of those reporting the age of first sex had their first sexual intercourse before 13 years. Compared to the Whites, Black/African Americans (13.2% vs 5.1%, OR=4.51, 95% CI: 2.78-7.31) and Hispanic young adolescents (8.3 % vs 5.1 %, OR=1.44, 95% CI=1.13-1,84) were more likely to report having early sexual intercourse. Males were more likely to report having multiple sexual partners than females (48.1% vs 36.5%, OR = 1.68, 95% CI = 1.22-2.29) and were more likely to report using condoms during the last sex compared to their female counterparts (59.7% vs 50.8%, OR = 1.43, 95% CI = 1.06-1.94). This study suggests the need for more research on young adolescents’ sexual behaviors and develop sexual health interventions that target preadolescence.

We systematically reviewed studies using wastewater for AMR surveillance in human populations, to determine: (i) the strength of the evidence for a wastewater-human AMR association, and (ii) methodological approaches which optimised identifying such an association, and which could be recommended as standard. We used Lin’s concordance correlation coefficient (CCC) to quantify agreement between AMR prevalence in wastewater and human compartments, and logistic regression to identify study features (e.g. sampling methods) associated with high-agreement (defined as wastewater-human AMR prevalences within ±10%). Of 8,867 records and 232 full-text methods reviewed, 29 studies were included. AMR prevalence data was extractable from 20 studies conducting phenotypic-only (n=11), genotypic-only (n=1) or combined (n=8) AMR detection. Overall wastewater-human AMR concordance was reasonably high for both phenotypic (CCC=0.81 [95% CI 0.74-0.87]) and genotypic comparisons (CCC=0.88 (95% CI 0.85-0.91)) despite diverse species-phenotypes/genotypes and study design. Logistic regression was limited by inconsistent reporting of study features, and limited sample size; no significant relationships between study features and high wastewater-human AMR agreement were identified. Based on descriptive synthesis, composite/flow-proportional sampling of wastewater influent, longitudinal sampling >12 months, and time/location-matched comparisons generally had higher-agreement. Further research and clear and consistent reporting of study methods is required to confirm optimal practice.

The platelet count, a component of the full blood count, has been identified as a useful diagnostic marker for cancer in primary care. The reference range for the platelet count is 150 to 400 or 450 × 109/l; this range does not account for natural variation in platelet count by age and sex. This study used three primary care cohorts from England Canada, and Australia. Patients aged 40 years and over with a full blood count were included and stratified by age (in 10-year bands), sex, (male/female), and platelet count group. Cancer incidence within one year of test date was estimated from linked registry data. In all three countries there was a clear upwards trend in cancer incidence with increasing platelet count, for both sexes and at all age groups. Lung and colorectal were the most common sites. These results have important implications for the international application of this work; analysis of local health datasets will be crucial to determine appropriate thresholds. Appropriate upper thresholds will depend on local populations, healthcare needs, and priorities. Further research is needed to assess the likely impact of new recommendations on the healthcare system, on cancer outcomes, and patient benefit.

The purpose of the study was to describe and compare the pharmacokinetics of five commercial edible marijuana products, determine the influence of body composition on pharmacokinetics, and, in light of epidemiology suggesting marijuana may offer diabetes protection, explore the influence of edible marijuana on glucose tolerance. Seven regular users of marijuana self-administered five edible products in a randomized crossover design; each product contained 10mg of delta-9-tetrahydrocannabinol (THC). 30-minutes following marijuana ingestion, participants imbibed a 75g glucose beverage. Time-to-peak plasma THC concentration ranged between 35 and 90 minutes; maximal plasma THC concentration (Cmax) ranged between 3.2 and 5.5 ng/mL. Differences between products in plasma THC concentration during the first 20-to-30 minutes were detected (P=0.019). Relations were identified between body composition and pharmacokinetic parameters for some products; however, none of these body composition characteristics were consistently related to pharmacokinetics across all five of the products. Edible marijuana had no effect on oral glucose tolerance compared with a marijuana-free control (Matsuda Index; P>0.395). Commercially available edible marijuana products evoke different plasma THC concentrations shortly after ingestion, but do not appear to influence acute glucose regulation. These data may allow marijuana users to make informed decisions pertaining to rates of edible marijuana ingestion and avoid overdose.

The oncogenes that are expressed in gliomas reprogram particular pathways of glucose, amino acid, and fatty acid metabolism. Mutations in isocitrate dehydrogenase genes (IDH1/2) in diffuse gliomas are associated with abnormally high levels of 2-hydroxyglutarate (2-HG) levels. The aim of this study was to determine whether metabolic reprogramming associated with IDH mutant gliomas leads to additional 1H MRS-detectable differences between IDH1 and IDH2 mutations and to identify metabolites correlated with 2-HG. A total of 21 glioma patients (age= 3711, 13 males) were recruited for MRS using a Semi-localization by adiabatic selective refocusing pulse sequence at ultra-high-field (7T). Tumour mutation subtype was confirmed by immunohistochemistry and DNA sequencing. LCModel analysis was applied for metabolite quantification. A two-sample t-test was used for metabolite comparisons between IDH1 (n=15) and IDH2 (n=5) mutant gliomas. The Pearson correlation coefficients between 2-HG and associated metabolites were calculated. A Bonferroni correction was applied for multiple comparison. IDH2 mutant gliomas have a higher level of 2-HG/tCho (total choline=phosphocholine+glycerylphosphorylcholine) (2.481.01vs.0.720.38, Pc<0.001) and myo-Inositol/tCho (2.700.90vs.1.460.51, Pc=0.011) compared to IDH1 mutation gliomas. Associated metabolites, myo-Inositol and glucose+taurine were correlated with 2-HG levels. These results show improved characterization of the metabolic pathways in IDH1 and IDH2 gliomas for precision medicine.

Background: Accidental caustic burns of the esophagus in children represent a significant global health challenge, often necessitating esophageal reconstruction. The aim of this study is to compare the efficacy and morbidity related to esophagus replacement with colonic and gastric tube transplants in a pediatric population followed for caustic stenosis. Method: This retrospective study was conducted at a tertiary pediatric surgery unit for children treated from January 1989 to December 2022. We compared colonic and gastric tube esophageal replacement. Short-term (within 30 days) and mid-term outcomes and complications were reviewed. Statistical evaluation was considered using a Chi-square test for categorical data analysis. Results: A total of 124 children with caustic esophageal burns were included. Among them, 23 (18.5%) had a gastric tube transplant for esophagus replacement and 101 (81.5%) a colonic transplant. During surgical intervention, we found a significantly higher risk of complications when using a colonic transplant (34%, p < 0.001). There was no significant statistical difference in postoperative short-term and mid-term complications between the two techniques. Twenty-six (26%) of the children required a reoperation, with a higher risk in the gastric tube transplant group (p < 0.001). Endoscopic dilatation after surgery was also performed on a higher number of children who had received a gastric tube transplant (p = 0.005). Overall, 97.6% recovered full normal oral feeding. Conclusions: We found that colonic and gastric tube replacement are both good options for pediatric esophageal replacement after a caustic injury and show effectiveness over time. Gastric tube transplants carried a slightly higher risk of reoperations and a higher number of dilatations post-surgery. However, our groups are not really comparable due to the much higher number of colonic transplants. Both surgical options have to be considered during surgery and the choice depends on the anatomy of the patient. Our future research will focus on assessing long-term quality of life and potential risk of neoplastic complications.

The interest in virtual fencing, as opposed to traditional physical barriers, has increased since it makes it easier to move the boundaries of animal enclosures for agricultural and rewilding purposes. Despite this, the implementation of virtual fence systems, such as the Nofence© system, requires large financial investments. The necessity of individual collars also makes it more difficult to implement this system on a larger scale. If a herd of cattle tend to maintain cohesive social groups around dominant individuals, it might be possible to use fewer collars thereby making the system more cost efficient. This study investigates the pattern in spatial distribution in a herd of 17 Angus cows on Fanø in Denmark with GPS locations, using a Nofence© system. The aim of this paper is to determine how individuals position themselves in a herd, spatially, and identify a pattern in ranks. The method used in this study examines the distances between an individual to the rest of the herd mates using nearest neighbour and distribution plots. Contrary to the expectations, this study did not show a distinct pattern in herd distribution. While some tendencies in spatial distribution patterns were observed, only a low concordance could be found (W=0.15,p=3.02e−16). Therefore, interactions among individuals should be considered in future studies, rather than only investigating the herd as one unit. A cumulative curves of the ranks estimated over the entire periods allowed however a rough estimation of the hierarchy and allowed the identification of the highest ranked cows. Therefore it might be possible to use fewer collars if the high ranked cows are discovered, but the estimation of the hierarchy will require a period of observation overall several days as the hierarchical positions are fluctuating too much from days to days. Therefore the cumulative rank curves seems to be a valid solution.

Ovine footrot is a complex multifactorial infectious disease, causing lameness in sheep with major welfare and economic consequences. Dichelobacter nodosus is the main causative bacterium, however, footrot is a polymicrobial disease with Fusobacterium necrophorum, Mycoplasma fermentans and Porphyromonas asaccharolytica also associated. There is limited understanding of the host response involved. Proinflammatory mediators interleukin (IL)-1β and C-X-C Motif Chemokine Ligand 8 (CXCL8) have been shown to play a role in the early response to D. nodosus in dermal fibroblasts and interdigital skin explant models. To further understand the response of ovine skin to bacterial stimulation, and to build the understanding of the role of the cytokines and chemokines identified in transcriptomic data, primary ovine interdigital fibroblasts and keratinocytes were isolated, cultured and stimulated with lipopolysaccharide (LPS), D. nodosus or F. necrophorum in the presence and absence of M. fermentans, whilst measuring mRNA expression and protein release of CXCL8 and, IL-1β. Stimulation with LPS, D. nodosus or F. necrophorum resulted in increased transcript levels of IL-1β and CXCL8 in M. fermentans free cells, however, only an increase in CXCL8 protein release was observed. No IL-1β protein release was detected despite increases in IL-1β mRNA, suggesting the signal for intracellular pre-IL-1β processing may be lacking when culturing primary cells in isolation. Keratinocytes and fibroblasts naturally infected with M. fermentans showed little response to LPS, a range of D. nodosus preparations or heat-inactivated F. necrophorum. Primary single cell culture models complement ex vivo organ culture models to study different aspects of the host response to D. nodosus. Ovine keratinocytes and fibroblasts infected with M. fermentans had a reduced response to experimental bacterial stimulation. However, in the case of footrot where Mycoplasma spp. are associated with diseased feet, this natural infection gives important insights into the impact of multiple pathogens on the host response.

Steroid analysis is important in the clinical assessment of endocrine function in health and disease. Although tandem mass spectrometry methods coupled with chromatographic separation are considered the gold standard analytical technique in this setting, enabling profiling of multiple steroids in a single sample, sample processing can be labour-intensive. Here we present a simple, efficient automated 96-well Supported Liquid Extraction method with dichloromethane/isopropanol as organic solvent, carried out on a Extrahera automated sample handler (Biotage), which completes sample preparation of 80 plasma samples (200µL) in 90 minutes. Compounds were separated on a Kinetex C18 column (150x3mm;2.6um) using a mobile phase of methanol and water (0.1% formic acid). The run time was 16 minutes on a Nexera uHPLC system (Shimadzu) with a QTrap 6500+ linear ion trap mass spectrometer (AB Sciex). Precisions ranged 8.1 to 18.1% RSD, bias -10.1-5.8%, and extraction recoveries 73.5-111.9%. LOQs ranged between 0.025–0.500 ng/mL.

Pyrethroid resistance is widespread in malaria vectors. However, differential mortality in discriminating dose assays to different pyrethroids is often observed in wild populations. When this occurs, it is unclear if this differential mortality should be interpreted as an indication of differential levels of susceptibility within the pyrethroid class, and if so, if countries should consider selecting one specific pyrethroid for programmatic use over another. A review of evidence from molecular studies, resistance testing with laboratory colonies and wild populations, and mosquito behavioural assays was conducted to answer these questions. Evidence suggests that in areas where pyrethroid resistance exists, different results in insecticide susceptibility assays with specific pyrethroids currently in common use (deltamethrin, permethrin, α-cypermethrin and λ-cyhalothrin) are not necessarily indicative of an operationally relevant difference in potential performance. Consequently, it is not advisable to use rotation between these pyrethroids as an insecticide resistance management strategy. Less commonly used pyrethroids (bifenthrin and etofenprox) may have sufficiently different modes of action, though further work would be needed to examine how this may apply to insecticide resistance management.

Ocular light exposure has important influences on human health and well-being through modulation of circadian rhythms and sleep, as well as neuroendocrine and cognitive functions. Current patterns of light exposure do not optimally engage these actions for many individuals, but advances in our understanding of the underpinning mechanisms and emerging lighting technologies now present opportunities to adjust lighting to promote optimal physical and mental health and performance. A newly developed, SI-compliant standard provides a way of quantifying the influence of light on the intrinsically photosensitive, melanopsin-expressing, retinal neurons that mediate these effects. The present report provides recommendations for lighting, based on an expert-scientific consensus and expressed according to this new measurement standard. These recommendations are supported by a comprehensive analysis of the sensitivity of human ‘non-visual’ responses to ocular light, are centred on an easily measured quantity (melanopic equivalent daylight (D65) illuminance), and provide a straightforward framework to inform lighting design and practice.

Synaptic transmission is essential for nervous system function and the loss of synapses is a known major contributor to dementia. Alzheimer’s disease dementia (ADD) is characterized by synaptic loss in the mesial temporal lobe and cerebral neocortex, brain areas associated with memory and cognition. The association of synaptic loss and ADD was established in the late 1980s and it has been estimated that 30-50% of neocortical synaptic protein is lost in ADD, but there has not yet been a quantitative profiling of different synaptic proteins in different brain regions in ADD from the same individuals. Very recently, PET imaging of synapses is being developed, accelerating the focus on the role of synaptic loss in ADD and other conditions. In this study, we quantified densities of two synaptic proteins, the presynaptic protein SNAP25 and the postsynaptic protein PSD95 in human brain using enzyme-linked immunosorbent assays (ELISA). Protein was extracted from the cingulate, hippocampus, frontal, visual, and entorhinal cortex from cognitively unimpaired controls, subjects with mild cognitive impairment (MCI) and demented subjects with different levels of Alzheimer’s pathology. SNAP25 is significantly reduced in ADD when compared to controls in frontal cortex, visual cortex and cingulate; while hippocampus showed a smaller, non-significant reduction and entorhinal cortex concentrations were not different. In contrast, all brain areas showed lower PSD95 concentrations in ADD when compared to non-demented controls, although in hippocampus this failed to reach significance. Interestingly, cognitively unimpaired cases with high levels of AD pathology had higher levels of both synaptic proteins in all brain regions. SNAP25 and PSD95 concentrations significantly correlated with densities of neurofibrillary tangles, amyloid plaques and Mini Mental State Examination scores. Our results suggest that synaptic transmission is affected by ADD in multiple brain regions. Differences were less marked in entorhinal cortex and hippocampus, most likely due to a ceiling effect imposed by the very early development of neurofibrillary tangles in older people in these brain regions.